The most recent information on IGF1R is here. Click here for the function of IGF1R. Edit this page in Wiki Genes - IGF1R or see Wiki Gene. The effect of IGF-I was mediated through the IGF-I receptor. Paper-1729740. Strikingly, SNCG physically interacted with IGF-IR and IRS-2. Paper-15402611. High MVP expression was related to high IGF1-R expression (p=0.023). Paper-12922634. IGF-IR knockdown or IGF-IR inhibitor repressed SNCG expression. Paper-15402611. Thus, hSOCS-2 interacted with IGF-IR both in vitro and in vivo. Paper-1574311. This was associated with an increase in the rate of SHP-2 recruitment to the IGF-IR. Paper-9522224. SHP-2 recruitment to IGF-IR was significantly attenuated by PRL co-treatment. Paper-14266448. Activation of IGFR occurs at least in part via SirT1- mediated repression of PTP1B. Paper-15102034. Both MDM2 and beta-arrestin co-immunoprecipitated with the IGF-1R. Paper-10750133. Direct interaction of insulin-like growth factor-1 receptor with leukemia-associated RhoGEF. Paper-8858392. Furthermore, KLF6 expression induced a significant increment in endogenous IGF-IR levels. Paper-10346476. IGFR-1 protein expression was associated with EGFR protein expression ( P = 0.03). Paper-13742732. Moreover, IGF-I and/or IL-4 induced long-term cell growth of the IGF-IR transfectants. Paper-1829658. We found that the IR is more efficient in interacting with the p85 than is the IGF-IR. Paper-518113. Most NSCLC tissues with EGFR overexpression had associated high levels of IGF-IR expression. Paper-13211759. This screen identified Receptor for Activated C Kinases ( RACK1) as an IGF-1R-interacting protein. Paper-9164730. ChIP assays showed enhanced E2F1- binding to the IGF-IR promoter in E2F1-expressing cells. Paper-14144187. In fact, Cav-1 and PTRF/Cavin co-immunoprecipitate with IGF-IR during receptor internalization. Paper-15558204. It decreases the protein levels of IGF-IR, IRS-1, and IRS-2 and increases the level of IGFBP-3. Paper-14659540. In summary, our data suggest that the IGF-IR gene is a novel downstream target for BRCA1 action. Paper-9883499. Expression of SRF or Igf1R partially reversed tumor suppressor function of miR-122. Paper-14166261. Among other candidate genes, DNA microarrays identified the IGF-IR gene as a putative E2F1 target. Paper-14144187. Transcriptional regulation of IGF-I receptor gene expression by the PAX3- FKHR oncoprotein. Paper-9145595. In summary, we have identified the IGF-IR gene as a novel downstream target for p63/p73 action. Paper-11196774. AR mutations alter the ability of the mutated protein to regulate IGF-IR expression. Paper-15124861. These data indicate that the IGF-I receptor is a physiological target for p53 in osteosarcoma cells. Paper-1333695. BRCA1 was able to suppress IGF-IR promoter activity both in the absence and presence of p53. Paper-10173619. The insulin-like growth factor I receptor- induced interaction of insulin receptor substrate-4 and Crk-II. Paper-8795316. Results of Western blots showed that BRCA1 induced a large reduction in endogenous IGF-IR levels. Paper-12575034. In summary, we have identified the IGF-IR gene as a novel downstream target for transcription factor KLF6. Paper-10346476. IGF-IR interacts directly with Caveolin-1 ( Cav-1), the most relevant protein of caveolae. Paper-15558204. The insulin-like growth factor-I receptor ( IGF-IR) mediates the biological actions of IGF-I and IGF-II. Paper-1744775. Insulin-like growth factor I receptor is expressed at normal levels in Nijmegen breakage syndrome cells. Paper-9523622. In these cells BRCA1 suppressed 45% of the Sp1- induced trans-activation of the IGF-I-R promoter. Paper-8487275. In summary, we identified the IGF-IR gene as a downstream target for Cav-1 action in breast cancer cells. Paper-12346565. This role of Mdm2 and p53 represents an unexpected mechanism for the regulation of IGF-1R and cell growth. Paper-9803904. ChIP analysis show enhanced AR binding to the IGF-IR promoter in AR-overexpressing cells. Paper-15124861. In conclusion, activation of IGF-IR mediates COX-2 expression in human pancreatic cancer cells. Paper-12611902. RESULTS: Results obtained showed that E2F1 expression induced a significant increment in endogenous IGF-IR levels. Paper-14144187. IGFII ligand binds IGFIR thereby initiating a signaling cascade which is both mitogenic and anti-apoptotic. Paper-15983754. Chromatin immunoprecipitation experiments suggested Notch-1 direct regulation of the IGF-1R promoter. Paper-15074857. Furthermore, HIF-1alpha suppression attenuated the serum deprivation- mediated increase in Akt and IGF-IR activation. Paper-13588922. Cav-1Y14F transfected cells showed a reduced internalization of IGF-IR compared with cells expressing wild type Cav-1. Paper-15558204. Syndecan-1 couples the insulin-like growth factor-1 receptor to inside-out integrin activation. Paper-15441681. Transcriptional regulation of IGF-I receptor gene expression by novel isoforms of the EWS- WT1 fusion protein. Paper-9409366. We found that the SH2 domain of CSK binds to the tyrosine- phosphorylated form of IGF-IR and IR. Paper-1758549. In conclusion, our data suggests that the IGF-IR gene is a physiologically relevant downstream target for BRCA1 action. Paper-12575034. Further investigation revealed that EGFR depletion induced enhancement of IGF1R ubiquitylation and degradation. Paper-13140520. Grb10 coprecipitates with the IGF-IR in cell lysates and is probably involved in the regulation of its activity. Paper-631739. We conclude that SOCS-3 binds to the IGFIR and may be a direct substrate for the receptor tyrosine kinase. Paper-8612732. These results raise the possibility that SOCS proteins may also play a regulatory role in IGF-I receptor signaling. Paper-1574311. Two splice variants of IR are expressed that enable formation of two isoforms of the IGF-IR/ IR hybrid receptor. Paper-12209367. However, IGF1R-independent effect of IGF-II on EVT cell migration required ROCKs but not RhoA, RhoC, Rac1, or Cdc42. Paper-12484244. IGF1R-dependent actions of IGF-II were confirmed by showing the effects of IGF1R-selective agonist Des1-3 IGF-I. Paper-12484244. We observed that the IGF-IR and IR associated with the C-terminal Src kinase ( CSK) following ligand stimulation. Paper-1758549. Furthermore, also IGF-I and IGF-II induced DNA synthesis was significantly suppressed by anti- IGF-IR mAb. Paper-9173896. On the other hand, BRCA1 enhanced IGF-IR levels in LNCaP C4-2 cells expressing an endogenous AR. Paper-13640086. Based on these findings, Cav-1 and PTRF/Cavin could represent two relevant and distinct targets to modulate IGF-IR function. Paper-15558204. The reciprocal regulation of gamma-synuclein and IGF-I receptor expression creates a circuit that modulates IGF-I signaling. Paper-15402611. ER-negative breast cancer cells often express low levels of the IGF-IR and fail to respond to IGF-I with mitogenesis. Paper-9065116. In vitro, IGF-IR-deficient Arg59Ter cells expressed less IGF-IR and unchanged insulin receptor ( IR) protein. Paper-12029601. Reintroduction of AR into PC-3 cells by stable transfection restored the androgen effect on IGF-IR up-regulation. Paper-11103833. MicroRNA-7 targets IGF1R ( insulin-like growth factor 1 receptor) in tongue squamous cell carcinoma cells. Paper-15440702. Interaction of Janus kinases JAK-1 and JAK-2 with the insulin receptor and the insulin-like growth factor-1 receptor. Paper-1333669. Human embryonic kidney cells (293) were transiently transfected with vectors containing IGF-IR and FLAG epitope-tagged hSOCS-2. Paper-1574311. The aim of the present study was to investigate whether the IGF-IR is a physiological target for p53 in osteosarcoma cells. Paper-1333695. Silencing of the IGF1R gene enhances sensitivity to DNA-damaging agents in both PTEN wild-type and mutant human prostate cancer. Paper-10798313. The present data suggests that the IGF-IR gene is a novel downstream target in an ATM-mediated DNA damage response pathway. Paper-10634510. Among ECM proteins tested only fibronectin and laminin but not vitronectin and collagen I stimulated trans-activation of IGF-IR. Paper-13430043. The C-terminal domain of IRRR was found to abolish binding in IR and IGFIR context, whereas other constructs bound ligands. Paper-2058083. We identified significant associations in variants in IGF1R and IRS1 in BRCA1 carriers and in IGFBP2 in BRCA2 carriers. Paper-14613819. Inhibition of wild-type P53 in HEPG2 cells by small interfering RNA (siRNA) significantly upregulated the expression of IGF1R. Paper-12454462. R1881-induced IGF-IR up-regulation was partially inhibited by the AR antagonist Casodex ( bicalutamide). Paper-11103833. The ChR was produced by fusing a MOG-specific single ‎chain antibody with the extracellular boundary of the IGF1R transmembrane segment. Paper-16034431. In hormone-responsive breast cancer cells, IGF-IR function is strongly linked with estrogen receptor ( ER) action. Paper-8446622. Effect of IGFBP-3 on IGF- and IGF-analogue- induced insulin-like growth factor-I receptor ( IGFIR) signalling. Paper-8905968. The p53- induced regulation of IGF-IR levels was studied in a tetracycline-regulated expression system. Paper-1333695. Interaction was abolished by knockdown of either receptor, and we noted that EGFR knockdown also suppressed IGF1R protein levels. Paper-13140520. In addition, IGF-I-induced IGF-IR and insulin receptor substrate-1 phosphorylation were greatly impaired in ATM-deficient cells. Paper-10634510. Elevated insulin-like growth factor-I receptor ( IGF-IR) levels in primary breast tumors associated with BRCA1 mutations. Paper-12575034. Elevated IGFIR expression regulating VEGF and VEGF-C predicts lymph node metastasis in human colorectal cancer. Paper-15117040. Regulation of insulin-like growth factor-I receptor gene expression by tumor necrosis factor-alpha and interferon-gamma. Paper-8976228. Most strategies have focused on targeting IGF1R alone without affecting IR levels given the known physiologic functions of IR. Paper-12396781. Our results are consistent with the proposal that HER3 has a structure similar to IGF-1R and binds ligand at a site in corresponding domains. Paper-9096132. Consequently, by sequestering Mdm2 in the cell nuclei, the level of p53 may indirectly influence the expression of IGF-1R. Paper-9803904. By binding to Hybrid-Rs(A), insulin activated the IGF-I half-receptor beta-subunit and the IGF-IR-specific substrate CrkII. Paper-9172387. Radioresistance could be induced by IGF-IR as long as the ability of the receptor to stimulate the MEK/ ERK pathway was retained. Paper-9844468. Furthermore, IGF-1R-dependent UVB- induced premature senescence required the phosphorylation of p53 serine 46. Paper-14305836. Thus, bFGF and IGF-I have differential effects on IGF-IR gene transcription, with the IGF-I response region as yet unidentified. Paper-932351. CONCLUSIONS: Levels of EGF-R, IGF-II, IGF-IR, and VEGF are significantly reduced following treatment with IGF-BP3 in cervical cancer. Paper-10151245. Caveolin-1 up-regulates IGF-I receptor gene transcription in breast cancer cells via Sp1- and p53-dependent pathways. Paper-12346565. Purified RACK1 or RACK1 WD1-4 associates directly with purified IR, IGF-1R, and STAT3 in vitro. Paper-10840945. An increased iNOS expression within the epithelial layer as well as increased number of iNOS- and IGF-1R-positive cells in NP was observed. Paper-14346563. Increased IGFR activity and glucose transport in cultured skeletal muscle from insulin receptor null mice. Paper-8988527. BRCA1 suppresses insulin-like growth factor-I receptor promoter activity: potential interaction between BRCA1 and Sp1. Paper-8487275. IGF-IR survival signaling is mediated through the downstream activation of phosphoinositide 3-OH kinase ( PI 3-K) and Akt. Paper-2035426. We find that GH induces formation of a complex that includes GHR, JAK2, and IGF-IR in these preadipocytes. Paper-10422464. Trichostatin A, a specific HDAC inhibitor, or p300 overexpression relieved the repression of IGF1R following oxidative stress. Paper-13426491. Dominant-negative JAK1 or JAK2 was able to block the IGF-IR-mediated tyrosine phosphorylation of STAT3 in 293T cells. Paper-8355222. Here we show that fibronectin, a major ECM component, engages insulin-like growth factor-I receptor ( IGF-IR) to inhibit PaCa cell death. Paper-13430043. Taken together, our results show that PTEN can regulate cell proliferation and apoptosis through inhibition of IGF-IR synthesis. Paper-10209874. The p53-family members p63 and p73 inhibit insulin-like growth factor-I receptor gene expression in colon cancer cells. Paper-11196774. Interestingly, autophosphorylation of IGFR induced by insulin and IGF-I was markedly increased in IR null skeletal myotubes. Paper-8988527. RACK1 also interacted with the IGF-1R in fibroblasts and MCF-7 cells and with endogenous insulin receptor in COS cells. Paper-9164730. The role of Shc and insulin-like growth factor 1 receptor in mediating the translocation of estrogen receptor alpha to the plasma membrane. Paper-10206258. Here we examined IGF-IR signaling and function in ER-negative MDA-MB-231 breast cancer cells and their IGF-IR-overexpressing derivatives. Paper-9065116. Here, we report that IGF-1 promotes the modification of IGF-1R by small ubiquitin-like modifier protein-1 ( SUMO-1) and its translocation to the nucleus. Paper-14244275. In contrast, the C and D domains of IGF-I allow higher affinity binding to the IGF-1R than the analogous domains of IGF-II. Paper-10646911. The data suggest IGF-IR as a key target for prevention of the prosurvival effects of ECM proteins and growth factors in pancreatic cancer. Paper-13430043. Delayed activation of insulin-like growth factor-1 receptor/Src/MAPK/ Egr-1 signaling regulates clusterin expression, a pro-survival factor. Paper-10791607. Elevated insulin-like growth factor 1 receptor, hepatocyte growth factor receptor and telomerase protein expression in mild ulcerative colitis. Paper-13042584. Here, we introduce new mechanisms through which proteins of the IGF-I/ IGF-IR signaling pathway may regulate ER function in the absence of ligand. Paper-14207316. Oestradiol enhances IGF-1R signalling by inducing the expression of insulin receptor substrate 1 ( IRS-1), a substrate of the IGF-1R. Paper-8972132. Insulin-like growth factor 1 receptor antibody induces rhabdomyosarcoma cell death via a process involving AKT and Bcl-x(L). Paper-15532869. Conversely, IGF-IR inhibitors may be of utility in suppressing the aberrant expression of SNCG in cancer cells and thereby block its pro-tumor effects. Paper-15402611. We In this study we have used the yeast two-hybrid system to compare the interaction of the cytoplasmic domains of the IR and the IGF-IR with p85. Paper-518113. We conclude that the interactions of SHC and IRS-1 with the IGFIR are similar to those which we have previously defined with the insulin receptor. Paper-273157. It has been hypothesized that IGFBP-3 inhibits IGF binding to the IGFIR via a mechanism independent of its ability to sequester IGFs. Paper-8905968. Coexpression experiments in M12 cells revealed that BRCA1 was able to suppress IGF-IR promoter activity and endogenous IGF-IR levels. Paper-13640086. Expression and activation of IGF-IR, in interleukin-3 (IL-3)-dependent 32Dcl.3 cells, prevents death under conditions of IL-3 withdrawal. Paper-1702116. All four hormones increased gene and/or protein expression of PSA, IGF-IR, IGF-I, and IGFBP-2 and decreased that of AR, ERbeta, IGF-II, and IGFBP-3. Paper-11271109. However, IGF-I- induced tyrosine-phosphorylation of IGF-I receptor and IRS-I and AKT phosphorylation were unaffected by ErbB2 overexpression. Paper-10206195. Localization of the insulin-like growth factor I receptor binding sites for the SH2 domain proteins p85, Syp, and GTPase activating protein. Paper-319693. Similarly, treatment with an anti- IGF-IR antibody effectively inhibited IGF-IR and MAPK/Erk activation and decreased COX-2 in parental cells. Paper-12611902. Several single-nucleotide polymorphisms of IGF1R, IGF2R, and IRS1 gene were significantly associated with tumor response to therapy and disease stage. Paper-15194158. The hSOCS-2 protein interacted strongly with the activated IGF-IR and not with a kinase negative mutant receptor in the two-hybrid assay. Paper-1574311. Interestingly, the stimulation of the IGF-IR transfectants with interleukin 4 ( IL-4) also resulted in strong mitogenesis independent of IRS expression. Paper-1829658. We could prove that Mdm2 physically associates with IGF-1R and that Mdm2 causes IGF-1R ubiquitination in an in vitro assay. Paper-9803904. Our results suggest that autocrine activation of the IGF-IR system significantly affects VEGF expression and angiogenesis in human pancreatic cancer. Paper-10028708. Finally, we demonstrated that a MAPK kinase inhibitor was able to suppress mitogenesis of the IGF-IR transfectants in response to IGF-I and/or IL-4. Paper-1829658. In vitro, activation of the IGF-IR/ IRS-1 pathway in ER-positive cells improves growth and counteracts apoptosis induced by anticancer treatments. Paper-9065116. In our in vitro model of CRC migration and invasion, uPA and uPAR appear to be downstream of IGF-IR and c-Met and are required for migration and invasion. Paper-10777532. Activation of IGF-1R by the chimeras reflected their binding affinities whereas the phosphorylation of the two IR isoforms was more complex. Paper-10646911. Importantly, this dominant-negative mutant was more efficient than wild type p55PIK in associating to IGF-IR and insulin receptor substrate-1 in 293 cells. Paper-1297758. These results support the concept of IGF1R targeting in prostate cancer, and indicate that PTEN loss does not render tumor cells refractory to this strategy. Paper-10798313. Consistent with these data, PTEN levels inversely correlated with levels of tyrosine- phosphorylated IGF-IR in tissue lysate arrays of primary breast cancers. Paper-13774361. In mouse P6 cells (overexpressing human IGF-1R) absence of beta-arrestin 1, but not of beta-arrestin 2, blocked ubiquitination of IGF-1R. Paper-10750133. In addition, IGF1R down-regulation increased insulin binding consistent with the formation of an increased number of holo- IR on the cell surface. Paper-12396781. IGF1R siRNA treatment diminished hybrid receptor formation, suggesting that specific down-regulation of IGF1R resulted in enhanced holo- IR formation. Paper-12396781. These findings suggest that inhibiting IGF-1R may be an effective therapeutic strategy for breast cancers that co-express IGF-1R and IRS-1 at high levels. Paper-13871949. Glutathione S-transferase- hSOCS-2 associated with activated IGF-IR in lysates of mouse fibroblasts overexpressing IGF-IR. Paper-1574311. Transactivation of CXCR4 by the insulin-like growth factor-1 receptor ( IGF-1R) in human MDA-MB-231 breast cancer epithelial cells. Paper-11055071. WT1 variants that contain the KTS insert are impaired in their ability to bind to the IGF-IR promoter and are unable to suppress IGF-IR promoter. Paper-9840798. Previously, we have shown that decorin core protein can bind to and activate insulin-like growth factor-I receptor ( IGF-IR) in endothelial cells. Paper-12832363. The present observations strongly suggest that AR activation may stimulate prostate cancer progression through the altered IGF-IR expression and IGF action. Paper-11103833. In addition, IGF-I could effectively induce the VEGF and VEGF-C mRNA expression and protein secretion in colorectal cancer cells expressing IGFIR molecules. Paper-15117040. IRR was expressed predominantly in neuroblastomas without MYCN gene amplification and coexpressed with IGF-1R, TrkA, and p75 neurotrophin receptor. Paper-10198586. In MCF7 cells, growth was inhibited by IGFIR antagonists but not by HER2 antagonists; however, HER2 antagonism enhanced the effect of IGFIR inhibitors. Paper-14289679. Insulin receptor substrate-2 mediated insulin-like growth factor-I receptor overexpression in pancreatic adenocarcinoma through protein kinase Cdelta. Paper-13618989. SK-N-MC cells were chosen for further investigation since they express IGF-I, IGF-I receptor and IGFBP-2 mRNA and secrete IGF-I and IGFBP-2 protein. Paper-11103179. Multiple WT1 binding sites were mapped in the 5'-flanking and 5'-untranslated regions of the IGF-I-R gene using gel retardation and DNaseI footprinting assays. Paper-842857. In BT474 cells, growth was inhibited by HER2 antagonists but not by IGFIR antagonists; however, IGFIR antagonists enhanced the effect of HER2 inhibitors. Paper-14289679. In this study we demonstrate that IRS-1, SHC, and the p85 subunit of phosphatidylinositol 3-kinase interact directly and specifically with the IGFIR. Paper-273157. Results of electrophoretic mobility shift assay showed that BRCA1 did not exhibit any specific binding to the IGF-IR promoter, although it prevented binding of Sp1. Paper-9883499. IGFIIR counterbalances these mitogenic and anti-apoptotic effects by binding, internalizing, and degrading IGFII thus making IGFII unavailable to activate IGFIR. Paper-15983754. To study whether WT1 could suppress the expression of the endogenous IGF-I-R gene, WT1-negative G401 cells were stably transfected with a WT1 expression vector. Paper-268096. Estrogen receptor regulates insulin-like growth factor-I receptor gene expression in breast tumor cells: involvement of transcription factor Sp1. Paper-12356378. To test whether or not SOCS-3 also binds to the IGFIR, we cloned human SOCS-3 by reverse transcription-polymerase chain reaction from human skeletal muscle mRNA. Paper-8612732. Insulin receptor substrate-1 ( IRS-1) and SHC become rapidly phosphorylated upon tyrosines after insulin-like growth factor I receptor ( IGFIR) activation. Paper-273157. Differential insulin-like growth factor I receptor signaling and function in estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 breast cancer cells. Paper-9065116. These results indicate that ESFT cell lines use an IGF-IR initiated signaling pathway through PI 3-K and Akt for survival when treated with doxorubicin. Paper-2035426. Insulin- stimulated metabolic genes and IR and IGF-IR are down-regulated, resulting in reduced insulin and IGF sensitivity and a delay in development. Paper-15346835. Here we demonstrate a novel role of RACK1 as an adaptor for insulin and insulin-like growth factor 1 receptor (IGF-1R)-mediated STAT3 activation specifically. Paper-10840945. CONCLUSIONS: We provide evidence that BRCA1 differentially regulates IGF-IR expression in AR-positive and AR-negative prostate cancer cells. Paper-13640086. These results suggest that BRCA1 is capable of suppressing the IGF-I-R promoter in a number of cell lines, thus resulting in low levels of receptor mRNA and protein. Paper-8487275. Recently, we have reported that stimulation of the IGF-I receptor in 293 HEK cells regulates interaction of the newly discovered IRS-4 molecule with the Crk family of proteins. Paper-8795316. Immunostainings were carried out for ER, Pser118ER, Her2, insulin growth factor receptor ( IGFR), p21-activated kinase 1 ( PAK1), pMAPK, bcl2 and progesterone receptor. Paper-12946197. pp120 ( Ceacam 1) undergoes ligand- stimulated phosphorylation by the insulin receptor, but not by the insulin-like growth factor 1 receptor ( IGF-1R). Paper-8457313. Evidence against a direct effect of leptin on insulin-like growth factor-I ( IGF-I), IGFBP-2 and IGF-I receptor expression in human SK-N-MC neuroepithelioma cells. Paper-11103179. In this study, we demonstrate an association between the IGF-I receptor and p85, Syp, and GAP, but not with PLC-gamma in lysates of cells overexpressing the human IGF-I receptor. Paper-319693. The present data show that inhibition of the IGF-IR transduction cascade augments the antipoliferative and proapoptotic effects of EGFR inhibition in colorectal cancer cells. Paper-14533512. Inhibition of cellular proliferation by the Wilms' tumor suppressor WT1 is associated with suppression of insulin-like growth factor I receptor gene expression. Paper-268096. Inhibition of internalization, via knockdown of the GTPase, dynamin-2, prevented not only IGF-IR dephosphorylation, but also PRL- enhanced IGF-IR phosphorylation. Paper-14266448. Insulin-like growth factor-I receptor ( IGF-IR) hyperstimulation induced hyperproliferation and antiapoptotic activities that were reversed by Akt2 down-regulation. Paper-11092396. But the role of IGF-II binding to the type 2 receptor is unclear, and it is now widely believed that the growth-promoting activities of IGF-II are also mediated via the IGF-I-R. Paper-1068221. The resistance of cells to apoptosis by IGF-1R signaling was mediated through MAPK and phosphatidylinositol 3-kinase ( PI3K) pathways and a yet unidentified pathway(s). Paper-8878730. Src family kinase activity was required for IGF-IR association with SHP-2, ligand-induced IGF-IR internalization, and PRL- enhanced IGF-IR phosphorylation. Paper-14266448. Furthermore, the enhanced cellular migration was abolished on incubation of MCF-7 and MCF-10A cells with function blocking antibodies directed at VN- binding integrins and the IGF-IR. Paper-12753017. In addition, an inverse correlation between BRCA1 and IGF-IR levels was observed in the androgen receptor (AR)-negative prostate cancer-derived P69 and M12 cell lines. Paper-13640086. Combined, our results suggest that WT1 suppresses IGF-IR gene transcription in breast cancer cells via a mechanism that involves protein-protein association with ERalpha. Paper-11243065. In this study, we show that inhibition of p53 causes ubiquitination and down-regulation, through increased degradation, of the IGF-1R in human malignant melanoma cells. Paper-9803904. For both receptors, deletion of the region containing the Y1322THM sequence in the IR and the Y1316AHM-similar sequence in the IGF-IR decreases their ability to interact with p85. Paper-518113. We show that IGF-IR internalization triggers Cav-1 and PTRF/Cavin translocation from plasma membrane to cytosol and increases IGF-IR interaction with these proteins. Paper-15558204. Inhibitors of SPCA1 may offer an alternative strategy to direct inhibitors of IGF1R and attenuate the processing of other proprotein convertase substrates important in basal breast cancers. Paper-15521265. Studies in mice suggest that this increase in apoptosis is related to the downregulation of the IGF1 receptor in the embryo associated with high IGF1 concentrations. Paper-13601076. Investigation of IGF1R-mediated signaling pathways using small interfering RNA approaches indicated that, as expected, phosphatidylinositol 3'-kinase ( PI3K) was activated by IGF1R. Paper-13018152. In severe inflammation, all parameters showed decreased epithelial expression; IGF1R showed decreased mRNA expression, while HGFR was overexpressed and TERT showed a decreased tendency. Paper-13042584. In 293 cells association of p55PIK with insulin receptor substrate-1 and with IGF-IR was dependent on PI 3-kinase, since it was increased by wortmannin, an inhibitor of PI 3-kinase. Paper-1297758. The WD repeat scaffolding protein RACK1 can mediate integration of the insulin-like growth factor I receptor ( IGF-IR) and integrin signaling in transformed cells. Paper-12007929. Activation of IR further enhanced the ability of Vav3 to induce membrane ruffles, but IGFR activation specifically promoted Vav3-mediated microspike formation. Paper-8578342. In this study, we assessed the potential role of insulin-like growth factor-I (IGF-I), the IGF-I receptor (IGF-IR) and IGF binding protein-2 ( IGFBP-2) in human colorectal cancer. Paper-8267455. Decorin regulates endothelial cell motility on collagen I through activation of insulin-like growth factor I receptor and modulation of alpha2beta1 integrin activity. Paper-12832363. We found that human SOCS-3 protein interacts directly with the cytoplasmic domains of the activated IGFIR and the insulin receptor ( IR) in the yeast two-hybrid assay. Paper-8612732. Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their phosphotyrosine-dependent interaction with the NPEY motif of the insulin-like growth factor I receptor. Paper-273157. Increased IGF-1R signaling mediated the growth factor independence of quiescent MIA PaCa-2 cells through the constitutive activation of mitogen-activated protein kinase ( MAPK). Paper-8878730. Membrane rafts segregate pro- from anti-apoptotic insulin-like growth factor-I receptor signaling in colon carcinoma cells stimulated by members of the tumor necrosis factor superfamily. Paper-10746446. Notch-1 activates Akt-1 through repression of phosphatase and tensin (PTEN) homolog expression and induction of the insulin-like growth factor 1 receptor ( IGF-1R). Paper-15074857. Overexpression or downregulation of RACK1 greatly enhances or decreases, respectively, IR/ IGF-1R- mediated activation of STAT3 and its target gene expression. Paper-10840945. The WT1 Wilms' tumor suppressor gene product interacts with estrogen receptor-alpha and regulates IGF-I receptor gene transcription in breast cancer cells. Paper-11243065. We conclude that IRS-2, unlike IRS-1, can interact with tyrosine-phosphorylated receptors such as the IR and insulin-like growth factor I receptor via multiple independent binding motifs. Paper-602535. In the present study in neuroblastoma, NDGA inhibits IGF-I- mediated activation of the IGF-IR and disrupts activation of ERK and Akt signaling pathways induced by IGF-I. Paper-12620104. Studies using IGF-I analogs determined this stimulation to be dependent on both heterotrimeric IGF-I-IGFBP- VN complex formation and the involvement of the IGF-I receptor ( IGF-IR). Paper-12753017. The results of Western analysis showed that KLF6 levels were higher in nontumorigenic P69 cells expressing high IGF-IR levels than in metastatic M12 cells containing reduced IGF-IR levels. Paper-10346476. These results are compatible with the notion that disruption of p63/p73- mediated signal transduction pathways in colon cancer may lead to increased IGF-IR gene transcription. Paper-11196774. We conclude that SHC and IRS-1 interact with the tyrosine- phosphorylated NPEY motif of the IGFIR, and that both proteins interact via related motifs located in their amino termini. Paper-273157. Transient transfections were used to evaluate IGF-IR promoter activity and chromatin immunoprecipitation (ChIP) assays were employed to assess E2F1- binding to the IGF-IR promoter. Paper-14144187. WT1 splice variants lacking a KTS insert between zinc fingers 3 and 4 suppressed IGF-IR promoter activity in the absence of p53 or in the presence of wild-type p53. Paper-9840798. Here we report the crystal structure of the first three domains (L1-CR-L2) of human IR at 2.3 A resolution and compare it with the previously determined structure of the corresponding fragment of IGF1R. Paper-12178709. Deletion analysis of the IGF-IR promoter revealed that a cluster of four GC boxes located between nucleotides -399 and -331 mediates a significant portion of the transactivating effect of KLF6. Paper-10346476. Our results showed that p53mt249 modulate IGF-II dependent IGF-IR signaling by upregulating IGF-IR and potentiating IGF-IRs where IGF-IRs became more sensitive on treatment with IGF-II. Paper-9930201. We hypothesize that one or more of these tyrosines are involved in the interaction between the SH2 domain of the Crk-II molecule when IRS-4 is phosphorylated upon IGF-I receptor activation. Paper-8795316. In conclusion we found that IGF-1R and PDGFR co-inhibition caused an increased cell death in two HGG cell line and induced the radiosensitization of the JNK1 expressing cell line. Paper-12604887. Hybrid receptors formed by insulin receptor ( IR) and insulin-like growth factor I receptor ( IGF-IR) have low insulin and high IGF-1 affinity irrespective of the IR splice variant. Paper-12209367. In contrast, a chimeric receptor comprising the extracellular portion of IGF-IR fused to the cytoplasmic tail of IR (chIR) fails to promote cell survival when activated with ligand. Paper-1702116. IGFIR is a member of the receptor tyrosine kinase family (3) Upon binding IGFII, IGFIR autophosphorylates tyrosine residues, thereby initiating signaling Fig. 1 ) (3). Paper-15983754. The GAP- GST binding site was confirmed by showing that a mutant IGF-I receptor with a deletion of the NPXY domain including tyrosine 950 was poorly precipitated by the GAP- GST. Paper-319693. Addition of a neutralizing antibody to IGF-I-R during PTH treatment under acidic conditions resulted in the abrogation of the ameliorative effect of PTH on endochondral differentiation. Paper-9925124. We have previously reported that the WT1 protein represses the expression of the IGF-I receptor gene, whereas the EWS(1-7)-WT1(8-10) fusion protein activates IGF-I receptor gene expression. Paper-9409366. Furthermore, deletion and bioinformatic analyses indicate that the ability of E2F1 to stimulate IGF-IR promoter activity was correlated with the number of E2F1 sites in the promoter region. Paper-14144187. In this study, we found co-expression of Insulin like growth factor-1 receptor ( IGF-1R) and platelet derived growth factor receptor ( PDGFR) in two high-grade gliomas (HGG) cell lines 18 and 38. Paper-12604887. Consistent with its tumor suppressor role, we demonstrated that BRCA1 repressed the activity of co-transfected IGF-IR promoter reporter constructs in a number of breast cancer-derived cell lines. Paper-9883499. Our results also showed that genistein induction of IGF-IR and IRS-1 expression resulted in enhanced tyrosine phosphorylation of IGF-IR and IRS-1 on IGF-I stimulation. Paper-10293636. Silencing of SNCG resulted in a decrease in ligand- induced phosphorylation of IGF-IR and its downstream signaling components, including insulin receptor substrate ( IRS), Akt, and ERK1/2. Paper-15402611. Our results suggest that in breast cancer cells, IGF-IR can control nonmitogenic processes regardless of the ER status, whereas IGF-IR growth-related functions may depend on ER expression. Paper-9065116. Results of transient coexpression experiments showed that all four predominant isoforms of WT1 (including or lacking alternatively spliced exons 5 and 9) repressed IGF-IR promoter activity by 39-49%. Paper-11243065. The interaction was specific for the insulin receptor and the insulin-like growth factor-1 receptor, and it required a catalytically active receptor kinase domain and an intact Grb10 SH2 domain. Paper-538540. Prolactin enhances insulin-like growth factor I receptor phosphorylation by decreasing its association with the tyrosine phosphatase SHP-2 in MCF-7 breast cancer cells. Paper-14266448. Because alphabeta chains of IGF1R and IR form hybrid receptors, we hypothesized that agents solely targeting IGF1R may affect tumor biology mediated by IGF1R/ IR hybrids and IR. Paper-12396781. To understand the structural importance of insulin-like growth factor I receptor ( IGF-IR) in mediating IL-4- and IGF-I-induced DNA synthesis, we transfected various mutants of IGF-IR to 32D cells. Paper-8997006. In this study we utilize the yeast two-hybrid system and assays of in vitro interaction to demonstrate that IRS-2 interacts directly with the IR and the insulin-like growth factor I receptor. Paper-602535. IL-4 stimulation of the IGF-IR transfectants resulted in enhanced tyrosine phosphorylation of SHC, Erk2, and signal transducer and activator of transcription 6 ( STAT6) proteins. Paper-1829658. We have carried out an amino acid residue conservation analysis in order to reconstruct the phylogeny of the IR Family. We have confirmed the location of ligand binding site 1 of the IGF1R and IR. Paper-14335869. The insulin receptor ( IR), the insulin-like growth factor 1 receptor ( IGF1R) and the insulin receptor-related receptor ( IRR) are covalently-linked homodimers made up of several structural domains. Paper-14335869. Altogether the data indicate that RACK1 is an IGF-1R- interacting protein that can modulate receptor signaling and suggest that RACK1 has a particular role in regulating Akt activation and cell survival. Paper-9164730. Moreover, we found that the insulin-like growth factor-1 receptor ( IGF-IR) bound to p55PIK; the interaction occurred at the receptor tyrosine 1316 and involved both p55PIK SH2 domains. Paper-1297758. Phosphorylation of the IGF-IR beta-subunit was obtained by IGF-I at 10(-10)-10(-8) mol/l and insulin at 10(-8) mol/l. Insulin and IGF-I at 10(-10)-10(-9) mol/l phosphorylated the IR beta-subunit. Paper-11103027. Tumor suppressor BRCA1 is expressed in prostate cancer and controls insulin-like growth factor I receptor ( IGF-IR) gene transcription in an androgen receptor-dependent manner. Paper-13640086. Furthermore, we find that inhibition of IGF-1R reduces p53 and Mdm2 translation through a gene-specific mechanism mediated by the respective 5' untranslated region of p53 and mdm2 messenger RNA. Paper-13430863. The results suggest that c-Src and CSK are involved in IGF-IR and IR signaling and that the interaction of CSK with the IGF-IR may play a role in the decrease in c-Src activity following IGF-I stimulation. Paper-1758549. In the present study, we examined the hypothesis that p63/p73 proteins may contribute to colon cancer cell proliferation via mechanism/ s that involve regulation of IGF-IR gene expression. Paper-11196774. The most obvious candidate genes within the regions identified by these linkages include the IGF1R on 15q and neuropeptide Y ( NPY) and growth hormone-releasing hormone ( GHRH) receptor on 7p. Paper-2117574. In conclusion, our results suggest that RGZ exerts an inhibitory effect on human ACC cell proliferation by interfering with the PI3K/Akt and ERK1/2 signaling pathways downstream of the activated IGF-IR. Paper-12960530. In addition, we demonstrated that transcriptional activation of the IGF-IR gene by Cav-1 requires an intact p53 signaling pathway, since Cav-1 was unable to elevate IGF-IR levels in p53-null cells. Paper-12346565. Down-regulated genes of note included pituitary adenylate cyclase-activating peptide ( PACAP), brain-derived neurotrophic factor ( BDNF), and insulin-like growth factor I receptor ( IGF-IR). Paper-11319586. Because IR also activates signaling pathways similar to IGF1R in breast cancer cells, agents targeting both receptors may be necessary to disrupt the malignant phenotype regulated by this growth factor system. Paper-12396781. These findings indicate that IGF-II acts via IGF-IR to enhance mitogenic signaling in pancreatic cancer cells and suggest that islet-derived IGF-II may contribute to pancreatic cancer cell growth in vivo. Paper-15975471. Immunocytochemistry using an alphaIR3 antibody confirmed the presence of IGF-I receptor in human blastocysts and the same antibody completely inhibited the stimulation of blastocyst formation by IGF-I. Paper-1729740. The present results provide the first evidence that IGFBP-3 may inhibit IGF binding to IGFR-1, and hence limit IGF action via a cellular mechanism that is different from the extracellular mechanism of sequestration. Paper-1249401. Here we provide evidence that beta-arrestin, otherwise known to be involved in the regulation of G protein-coupled receptors, serves as an adaptor to bring the oncoprotein E3 ubiquitin ligase MDM2 to the IGF-1R. Paper-10750133. The aim of this study was to investigate the prognostic role of insulin-like growth factor-1 receptor (IGF-1R) and IGF binding protein-3 ( IGFBP-3) in patients with squamous cell carcinoma of the head and neck (SCCHN). Paper-16096963. These results suggest that GH- induced formation of the GHR- JAK2- IGF-IR complex is governed instead by GH-dependent conformational change(s) in the GHR and/or JAK2. Paper-10422464. Interestingly, we observed that the carboxyl- terminal domain of the IGF-IR associates only with the p85 c-SH2 domain, whereas the corresponding domain of the IR interacts with both the n-SH2 and the c-SH2 domains. Paper-518113. The ability of BRCA1 to regulate IGF-I receptor ( IGF-IR) expression was studied by coexpression experiments using a BRCA1 expression vector along with an IGF-IR promoter-luciferase reporter. Paper-13640086. In summary, we provide evidence that activated wt AR enhances IGF-IR transcription in prostate cancer cells via a mechanism that involves AR binding to the IGF-IR promoter. Paper-15124861. In contrast to the usual physiologic situation in which following IGF-I exposure SHP-2 is recruited to IGF-IR via SHP-2 substrate-1 (SHPS-1) in the presence of echistatin, SHPS-1 was not used for SHP-2 recruitment. Paper-9522224. Primary culture of trophoblast cells, which express IGF-IR, IR, and HR, were exposed to TNF-alpha, and the effects of IGF-I in stimulating trophoblast cell proliferation and migration were determined. Paper-14772406. Our data demonstrate that small interfering RNA-driven elimination of MR in cardiac fibroblasts does not inhibit aldosterone- induced IGF-IR phosphorylation and subsequent increase in elastin production. Paper-13824937. The insulin-like growth factor-I receptor ( IGF-IR), c-Kit, vascular endothelial growth factor receptor ( VEGFR) and epidermal growth factor receptor ( EGFR) have been identified as potential drug targets in SCLC. Paper-13249772. Initial attempts based on fusion of the luciferase to IGFR, and EYFP to IGFR, or to downstream signaling molecules, insulin receptor substrate-1 ( IRS1) or protein tyrosine phosphatases-1B ( PTP-1B), failed. Paper-11016388. This decrease in IGF-1 receptor may confer a survival advantage to prostate cancer cells that have entered the circulation by making them resistant to the differentiative effects of IGF-1 at metastatic sites such as bone. Paper-10654763. Interestingly, down-regulation of Akt2 suppressed the EMT-like morphological conversion induced by Akt1 down-regulation in IGF-IR-overexpressing cells and inhibited migration in EGF-stimulated cells. Paper-11092396. Recently, p53 was demonstrated to affect the expression of the insulin-like growth factor 1 receptor ( IGF-1R), a receptor tyrosine kinase that plays a crucial role in growth and survival of cancer cells. Paper-9803904. The subcellular localization of the mature protein analogs for EGFR, FGFR, IGFR, RAR beta, and BFGF were identified using fluorescence immunocytochemistry and confocal laser scanning microscopy. Paper-738401. Our results suggest that prostate cancer progression is associated with a decrease in IGF-IR expression that could be the result of impaired ability of AR to stimulate IGF-IR gene expression. Paper-15124861. Expression of transferrin receptors, type-1 insulin-like growth factor receptors ( IGF1R), and interleukin 4 receptors ( IL4R) was measured by flow cytometry analysis on unirradiated cells and on cells 3 to 120 h after irradiation. Paper-9939145. Measurement of the 50 most highly regulated genes by quantitative PCR did not reveal a single gene regulated uniquely via the IR or IGF1R using cells expressing exclusively IGF-1 or insulin receptors. Paper-15125528. Coimmunoprecipitation experiments showed that p53 and WT1 physically interact, whereas electrophoretic mobility shift assay studies revealed that p53 modulates the ability of WT1 to bind to the IGF-IR promoter. Paper-9840798. Consistently, PRL diminished IGF-I- induced IGF-IR internalization, which may result from reduced SHP-2 association with IGF-IR, because we demonstrated an essential role for SHP-2 in IGF-IR internalization. Paper-14266448. ARF suppressed gene transcription for renal cortical and medullary IGF-IR and some IGFBPs. rhIGF-I independently affected some renal cortical or medullary IGFBP mRNAs. rhIGF-I increased hepatic IGFBP-2 mRNA and serum IGFBP-2. Paper-1666086. In conclusion, our data demonstrate that OxLDL downregulates IGF-1R via redox-sensitive pathways that are distinct from OxLDL signaling through MAPK- and PPARgamma-involved pathways but may involve a CD36-dependent mechanism. Paper-10970828. CONCLUSIONS: In summary, we provide evidence that E2F1 regulates IGF-IR gene transcription in prostate cancer cells via a mechanism that involves direct binding to specific elements in the proximal IGF-IR promoter. Paper-14144187. These results suggest that underexpression, deletion, or mutation of WT1 may result in increased expression of the IGF-IR, whose activation by IGF-II may be an important aspect of the biology of Wilms tumor. Paper-7806254. In particular, IGF-IR appears to couple IRS-1 preferentially to Grb2 whereas, in contrast, IR appears to couple IRS-1 preferentially to the p85 subunit of phosphatidyl inositol 3-kinase (PI3-kinase) and to Nck. Paper-8948586. [35S]methionine pulse experiments in PC3 cells overexpressing PTEN demonstrated that these cells synthesize significantly lower levels of the IGF-IR precursor, whereas PTEN overexpression had no effect on IGF-IR degradation. Paper-10209874. Targeting the MAPK pathway through downstream MAPK/ extracellular signal-regulated kinase kinase (MEK) antagonism similarly promoted IGF-driven pAkt and synergism with IGF-IR inhibition. Paper-13035955. Collectively, these data show that resistance to inhibition of MEK, mTOR, and EGFR is associated with enhanced IGF-IR-directed Akt signaling, where all affect feedback loops converging at the level of IRS-1. Paper-13035955. A chimeric receptor of the insulin-like growth factor receptor type 1 (IGFR1) and a single chain antibody specific to myelin oligodendrocyte glycoprotein activates the IGF1R signalling cascade in CG4 oligodendrocyte progenitors. Paper-16034431. We confirmed that STAT5b, cyclin D1, and IGF-1R is up-regulated by hypoxia, and the increased STAT5b binds strongly to the STAT5-binding sites contained within the distal 5'-flanking region of IGF-1 gene in breast cancer cells. Paper-14700206. Furthermore wild type IGF-1 mediated co-precipitation of alphavbeta3 and IGF1R, whereas the R36E/R37E mutant did not, suggesting that IGF-1 mediates the interaction between alphavbeta3 and IGF1R. Paper-13961778. Conversely IGF-1 receptor ( IGF-1-R), transforming growth factor-beta 2 ( TGFB-2), TGFB-2 receptor (TGFB-2-R), 17 beta-hydroxysteroid dehydrogenase (17-B-HSD) and leukemia inhibitory factor ( LIF) levels were up-regulated in PcDNA. Paper-582305. Because of the sequence homology and tertiary structure similarities between proinsulin (PI) and insulin-like growth factor-I (IGF-I), it is possible that PI interacts with the IGF-I receptor with higher affinity than insulin. Paper-7161526. Ataxia-telangiectasia mutated gene controls insulin-like growth factor I receptor gene expression in a deoxyribonucleic acid damage response pathway via mechanisms involving zinc-finger transcription factors Sp1 and WT1. Paper-10634510. CONCLUSIONS: Blocking Hsp90 disrupts IGF-I and IL-6- induced proangiogenic signaling cascades by targeting IGF-IR and STAT3 in pancreatic cancer, leading to significant growth-inhibitory effects. Paper-12591181. Signaling through the IGF-I receptor ( IGF-IR) has been shown to stimulate the growth and motility of a wide range of cancer cells. γ-synuclein ( SNCG) is primarily expressed in peripheral neurons but also overexpressed in various cancer cells. Paper-15402611. Based on our findings, we propose that CXCR4 constitutively forms a complex with IGF-1R in MDA-MB-231 cells, and that this interaction allows IGF-1 to activate migrational signaling pathways through CXCR4, G(i)alpha2 and Gbeta. Paper-11055071. Site-specific mutants of IR and IGF-1R impaired in RACK1 binding are ineffective in mediating recruitment and activation of STAT3 as well as in insulin- or IGF-1-induced protection of cells from anoikis. Paper-10840945. Taken together, our findings indicate that RACK1 enhances IGF-I- mediated cell migration through its ability to exclusively associate with either beta1 integrin or PP2A in a complex at the IGF-IR. Paper-12007929. Furthermore, transfection of the chimera induced a significant increase in the endogenous levels of IGF-I-R protein, suggesting that the IGF-I-R gene is a physiologically-relevant molecular target for the PAX3- FKHR oncogene. Paper-9145595. In this study, we identify insulin-like growth factor-1 receptor as a binding partner of Loop 6/ TIMP-2 and characterize this interaction on the endothelial cell surface and the consequences of this interaction on downstream receptor signaling. Paper-15571241. Single IGF-IR knockdown inhibited IGF-I-dependent phosphorylation of AKT but had no effect on IGF-I- or EGF-dependent phosphorylation of ERK1/2, indicating a role of EGFR in ligand-dependent ERK1/2 phosphorylation. Paper-14533512. We conclude that deletion of the carboxyl region of the Gag- IGFR inactivates, instead of activating as in the case with Gag- IR, its transforming activity and the amino acid sequence 1250 to 1310 is essential for PTK and transforming activities. Paper-7847266. A positive relationship was apparent between the amount of IGF-1-R with ER and PR (Spearman; 2P less than 0.02 and 2P less than 0.01, respectively; n = 32), whereas for EGF-R a negative relationship was observed (for both 2P less than 0.01; n = 44). Paper-6475824. Moreover, complex formation does not appear dependent on GH- induced activation of the ERK or phosphatidylinositol 3-kinase signaling pathways or on the tyrosine phosphorylation of GHR, JAK2, or IGF-IR. Paper-10422464. Transient IGF1R knockdown induced enhanced phosphorylation of the EGFR and its effectors JNK, ERKs and STAT5, but this did not prevent apoptosis induction and inhibition of clonogenic survival following IGF1R knockdown. Paper-13140542. The levels of IGF-I-R mRNA in the tumors were sixfold higher than in normal adjacent kidney tissue and were inversely correlated to the levels of WT1 mRNA, suggesting that the expression of the IGF-I-R gene is under inhibitory control by WT1. Paper-842857. OBJECTIVE: Analysis of polymorphisms in the genes of IGF1, IGF1 receptor ( IGF1R) and the negative regulator of the cardiac IGF1 signalling pathway, myostatin ( MSTN), and their relation to left ventricular mass (LVM) of endurance athletes. Paper-14103111. The fraction of IGF-I binding sites behaving as hybrids (anti- IR- bound/anti- IGFR-bound) was approx. 40% in liver and spleen, 70% in placenta, and 85-90% in skeletal muscle and heart, similar results being obtained in rabbit and human tissues. Paper-1222427. Substrate-bound insulin-like growth factor (IGF)-I-IGF binding protein- vitronectin- stimulated breast cell migration is enhanced by coactivation of the phosphatidylinositide 3-Kinase/ AKT pathway by alphav-integrins and the IGF-I receptor. Paper-12753017. Neither CXCR4 knockdown nor PTX had any effect on the ability of IGF-1 to activate IGF-1R, suggesting that CXCR4 and G proteins are activated subsequent to, or independently of, phosphorylation of IGF-1R by IGF-1. Paper-11055071. To examine the potential interplay between WT1 and ERalpha in control of IGF-IR gene transcription we employed ER-depleted C4 cells that were generated by clonal selection of ER-positive MCF-7 cells that were maintained in estrogen-free conditions. Paper-11243065. Using fibroblasts from the Minn-1 leprechaun, we have now investigated the expression of three different growth factor receptor genes: the IR, the insulin-like growth factor-I receptor ( IGF-IR), and the epidermal growth factor receptor ( EGFR). Paper-7354963. The genes for insulin-like growth factor 1 receptor ( IGF1R), aggrecan ( AGC1), beta2-microglobulin (B2M), and an H6-related gene have been mapped to a single chicken microchromosome by genetic linkage analysis. Paper-1040638. The hp55 gamma protein interacts strongly with the activated IGFIR but not with the kinase-negative mutant receptor. hp55 gamma also interacts with the insulin receptor ( IR) in the yeast two-hybrid system. Paper-1401807. Inhibition of SPCA1 produced a pronounced alteration in the processing of insulin-like growth factor receptor ( IGF1R), with significantly reduced levels of functional IGF1Rβ and accumulation of the inactive trans-Golgi network pro- IGF1R form. Paper-15521265. The CIM6PR/ IGF2R locus in man is asyntenic with the genes encoding IGF-II ( IGF2), the IGF-I receptor ( IGF1R), and the cation-dependent mannose 6-phosphate receptor ( CDM6PR). Paper-6107193. We also examined associations with four common functional polymorphisms of genes involved in aspects of the GH-IGF system--the IGF1 receptor ( IGF1R), insulin receptor substrate ( IRS1), growth hormone ( GH1), and IGF binding protein-3 ( IGFBP3). Paper-12385132. Aldosterone stimulates elastogenesis in cardiac fibroblasts via mineralocorticoid receptor-independent action involving the consecutive activation of Galpha13, c-Src, the insulin-like growth factor-I receptor, and phosphatidylinositol 3-kinase/Akt. Paper-13824937. Growth hormone ( GH) status regulates GH receptor and GH binding protein mRNA in a tissue- and transcript-specific manner but has no effect on insulin-like growth factor-I receptor mRNA in the rat. Paper-564686. Taken together, these results suggest that a novel potential mechanism by which TNF-alpha and IFN-gamma affect cellular proliferation involves suppression of IGF-l-R promoter activity, as well as destabilization of IGF-l-R transcripts. Paper-8976228. ADAM10 (a distintegrin and metalloprotease family 10), serum response factor ( SRF), and insulin-like growth factor 1 receptor ( Igf1R) that promote tumorigenesis were validated as targets of miR-122 and were repressed by the microRNA. Paper-14166261. Coprecipitation studies revealed the presence of a constitutive complex containing IGF-1R, CXCR4, and the G protein subunits, G(i)alpha2 and Gbeta, and stimulation of MDA-MB-231 cells with IGF-1 led to the release of G(i)alpha2 and Gbeta from CXCR4. Paper-11055071. In conclusion, p53 regulates IGF-IR expression, as reflected by a reduction in IGF-IR protein and a parallel reduction in IGF-I-induced tyrosine phosphorylation of the IGF-IR and IRS-1 in an osteosarcoma cell line. Paper-1333695. We conclude that RACK1 mediates recruitment of STAT3 to IR and IGF-1R specifically for activation, suggesting a general paradigm for the need of an adaptor in mediating activation of STATs by receptor protein tyrosine kinases. Paper-10840945. The prognostic significance, as well as the relationship with known prognostic factors in breast cancer, of insulin-like growth factor 1 receptor ( IGF-1-R), epidermal growth factor receptor ( EGF-R), and somatostatin receptor ( SS-R) was evaluated. Paper-6449423. We have utilized immunohistochemistry to compare the intratumoral IGF-I and IGF-I receptor ( IGF-IR) protein expression in 57 BRCA1/2 mutation carriers and 102 matched breast cancer patients without a family history in a nested case-control study. Paper-13435311. MATERIAL AND METHODS: Tissue microarrays (TMAs) made of biopsy samples from 20 mildly, 20 moderately and 20 severely active UC, 12 non-specific colitis (NSC) and 20 healthy colon were prepared, and immunolabelled with anti-EGFR, - IGF1R, -HGFR, -CDX2, - CK antibodies. Paper-14676717. We investigated cell survival ( cell count), proliferation (CD71-FACS), apoptosis (Annexin-V-FACS, Caspase-3 activity, PCD) and anti-apoptosis (112-Ser Bad phosphorylation), and regulation of IGF-I receptor surface expression ( IGF-I receptor-FACS). Paper-10173623. The interaction of all three proteins is dependent upon IGFIR kinase activity and, furthermore, substitution of Tyr-950 with Phe within the NPEY motif of the IGFIR eliminated interaction with both SHC and IRS-1 but had no effect upon p85 interaction. Paper-273157. We propose that induction of decorin expression in angiogenic, as opposed to quiescent, endothelial cells promotes a motile phenotype in an interstitial collagen I-rich environment by both signaling through IGF-IR and influencing alpha2beta1 integrin activity. Paper-12832363. It is plausible that reciprocal EGFR compensation could mediate resistance to IGF1R inhibition, prompting us to investigate effects of IGF1R depletion on EGFR signaling in breast cancer cells expressing relatively high (MDA-MB-468) or low (MCF7) EGFR. Paper-13140542. This study provides the first mechanistic insights into the action of IGF-I-IGFBP- VN complexes and adds further evidence to support the involvement of VN- binding integrins and their cooperativity with the IGF-IR in the promotion of tumor cell migration. Paper-12753017. There was no significant difference between NBS and NBS1-complemented cells in activation of major downstream pathways of IGF-IR upon IGF-I stimulation, including phosphatidylinositol-3(') kinase ( PI3-K) and mitogen-activated protein kinase ( MAPK). Paper-9523622. These results demonstrate that the activation state of alphaVbeta3 is an important regulator of the duration of IGF-IR phosphorylation and subsequent downstream signaling and that this regulation is mediated through changes in the subcellular localization of SHP-2. Paper-9522224. Combined IGF-IR and EGFR silencing by either siRNAs or tyrosine kinase inhibitors diminished the phosphorylation of downstream signaling pathways AKT and extracellular signal-regulated kinase (ERK)-1/2 more effectively than did the single receptor knockdown. Paper-14533512. These findings indicate that IGF-I utilizes a novel EGFR-dependent signaling pathway involving the formation of a complex between the IGF-IR and the EGFR to activate the ERK pathway and to stimulate proliferation in normal human mammary epithelial cells. Paper-10209794. Augmentation of basal IGF-I receptor phosphorylation was associated with coordinate increases in basal tyrosine phosphorylation of insulin receptor substrate (IRS)-2 and activation of Erk, which were also minimally responsive to IGF-I stimulation. Paper-12753010. Since many of the actions of IGF-II are mediated through activation of the IGF-I receptor ( IGF-IR), we have measured the levels of IGF-IR mRNA in normal kidney and in Wilms tumor samples using solution hybridization/RNase protection assays. Paper-7806254. METHODS: Samples from 964 postmenopausal Norwegian women aged 55-71 years were collected as a part of the Tromsø Mammography and Breast Cancer Study. All samples were genotyped for 25 SNPs in IGF1, IGF2, IGF1R, IGF2R, IGFALS and IGFBP3 using Taqman (ABI). Paper-15237012. We propose that (i) the IGF-IR and the IR share at least in part the same molecular mechanism underlying their interplay with their two substrates, p52Shc and IRS-1, and (ii) IRS-1 interacts with the IGF-IR in a fashion that is different from that used by p52Shc. Paper-377093. We propose that RMS pathogenesis involves increased IGF1R expression that enhances AKT and Bcl-x(L)-mediated cell survival, and the blockage of IGF1R results in inhibition of survival signal from Bcl-x(L) and cell death in the sensitive Bcl-2 negative cells. Paper-15532869. Our results show that overexpression and activation of IGF-IR reduced PKC-alpha expression, PKC activity, and downstream ERK1/2 signaling, and these effects were reversed in cells expressing kinase (Y(1131,1135,1136)F) or C-terminal (Y(1250/51)F) domain mutants of IGF-IR. Paper-14084716. However, inclusion of curcumin to continued FOLFOX treatment for another 48 h greatly reduced the survival of these cells, accompanied by a concomitant reduction in activation of EGFR, HER-2, IGF-1R and AKT, as well as expression of COX-2 and cyclin-D1. Paper-14678800. In this study, we explore interactions between GHR- JAK2 and IGF-IR signaling pathway elements utilizing the GH and IGF-I-responsive 3T3-F442A and 3T3-L1 preadipocyte cell lines, which endogenously express both the GHR and IGF-IR. Paper-10422464. This effect was associated with significant reductions in the levels of IGF-l-R mRNA and protein, and with inhibition of IGF-l-R promoter activity, suggesting that TNF-alpha and IFN-gamma affect IGF-l-R gene expression at the transcriptional level. Paper-8976228. In this study, we discovered that 2-DG treatments disrupted the binding between insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3 ( IGFBP3) so that the free form of IGF-1 could be released from the IGF-1.IGFBP3 complex to activate IGF-1 receptor ( IGF1R) signaling. Paper-13948007. The progression of prostate cancer from an organ-confined, androgen-sensitive disease to a metastatic one is associated with dysregulation of androgen receptor (AR)- regulated target genes and with a decrease in insulin-like growth factor-I receptor ( IGF1R) expression. Paper-15107064. Collectively, these results show that IGF-IR can inhibit PKC-alpha gene transcription and thereby block the synthesis of PMA-regulated MMPs, suggesting that within the same cells, IGF-IR can act as both a positive and negative regulator of MMP expression and function. Paper-14084716. Individuals underwent biopsy of the right vastus lateralis muscle, and real-time polymerase chain reaction ( PCR) amplification of mRNAs for insulin-like growth factor-I ( IGF-I), IGF-II, IGF-I receptor ( IGF-IR), IGF-IIR, and myostatin (44 patients) was performed. Paper-10774302. To assess the potential interactions between KLF6 and p53 in the regulation of IGF-IR gene expression, transfections were performed in the colorectal cancer cell line HCT116(+/+), which expresses p53, and its HCT116(-/-) derivative, which lacks p53. Paper-10346476. A monoclonal antibody (alpha IR3) that blocks ligand binding to the insulin-like growth factor I (IGF-I) receptor ( IGF-IR) inhibited IGF-II-mediated growth stimulation, and IGF-II enhanced insulin-receptor substrate 1 ( IRS-1) phosphorylation. Paper-15975471. Characteristic alterations detected in HCC and hepatoma cell lines comprise the increased expression of IGF-II and the IGF-I receptor ( IGF-IR), which have emerged as crucial events in malignant transformation and the growth of tumours. Paper-8972130. CONCLUSION: Parathyroid hormone at low concentration stimulates the differentiation and proliferation of cartilage cells and prevents the suppressive effect of acidosis on endochondral bone differentiation and on the IGF-I/ IGF-I-R system in skeletal growth centers. Paper-9925124. Grb10 interacts differentially with the insulin receptor, insulin-like growth factor I receptor, and epidermal growth factor receptor via the Grb10 Src homology 2 (SH2) domain and a second novel domain located between the pleckstrin homology and SH2 domains. Paper-1372156. Previous studies have proposed that the two receptors interact directly with the SH2 domains of the Mr 85K regulatory subunit ( p85) of PI 3- kinase via phosphorylated Y1322THM and Y1316AHM sequences located in the carboxyl-terminal domain of the IR and the IGF-IR, respectively. Paper-518113. The present study was aimed at evaluating the hypothesis that IGF-IR gene transcription in breast cancer cells is under inhibitory control by WT1 and, furthermore, that the mechanism of action of WT1 involves functional and physical interactions with estrogen receptor-alpha (ERalpha). Paper-11243065. This dissociation of PP2A from RACK1 and an IGF-I- mediated decrease in cellular PP2A activity did not occur in cells expressing either the serine 1248 or tyrosine 1250/1251 mutants of the IGF-IR that do not interact with RACK1. Paper-12007929. The effects of irradiation on Pthr1, CTGF, IGF2 and CXCL12 in PZ and Pthr1, CTGF, IL17b and IGF1R in the HZ determined by microarray and real-time RT-PCR was highly correlated ( r = 0.797, p < 0.05 in the PZ and r = 0.875, p < 0.01 in the HZ, respectively). Paper-13424397. Cav-1 and PTRF/Cavin silencing by siRNA differently affect surface IGF-IR levels following IGF1 treatment: Cav-1 and PTRF/Cavin silencing significantly affect IGF-IR rate of internalization, while PTRF/Cavin silencing also decreases IGF-IR plasma membrane recovery. Paper-15558204. The IGF1R binds IGF1 and IGF2 with high affinity and the IR binds insulin with high affinity; however, since both receptors share a high degree of structural and functional homology, the IGF1R can bind insulin and the IR can bind the IGFs with reduced affinity. Paper-13122487. The progression of prostate cancer from an organ-confined, androgen-sensitive disease to a metastatic one is associated with dysregulation of androgen receptor (AR)- regulated target genes and with a decrease in insulin-like growth factor-I receptor ( IGF-IR) expression. Paper-15124861. Single nucleotide polymorphisms ( SNPs) in the ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL genes were associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2D) in the Finnish Diabetes Prevention Study (DPS). Paper-14500636. Basal and GH stimulated phosphorylated (p-) JAK2 and STAT5 levels were similar in controls (C) and D. The levels of p- IGF1R were similar in the two groups at baseline, while pAkt, pGSK3, p-mTOR, p-rpS6, p-erk1/2 (Mapk), and pSTAT-3 were increased in D. Paper-13875578. EGFR and IGF-1R interact on multiple levels, either through a direct association between the two receptors, by mediating the availability of each others ligands, or indirectly, via common interaction partners such as G protein coupled receptors ( GPCR) or downstream signaling molecules. Paper-13993038. Cotransfection of Chinese hamster ovary cells with rat and human IGF-IR gene promoter constructs driving luciferase reporter genes and with WT1 expression vectors showed that the active WT1 gene product represses IGF-IR promoter activity in a dose-dependent manner. Paper-7806254. Mutation of receptor tyrosines 950, 1250, 1251, and 1316 to phenylalanine or deletion of the COOH-terminal 93 amino acids did not result in decreased interaction of the receptor with hSOCS-2 protein. hSOCS-1 protein also interacted strongly with IGF-IR in the two-hybrid assay. Paper-1574311. Our data suggest that enhanced synthesis of survivin protein mediated by the IGFR/ EGFR heterodimer counteracts the antitumor action of erlotinib, indicating the needs of integration of IGF-IR- targeted agents to the treatment regimens with EGFR TKI for patients with lung cancer. Paper-12275358. Given that the IGF1R gene has been identified as a downstream target for AR action, our data is consistent with a model in which the AR gene undergoes methylation during progression of the disease, leading to dysregulation of AR targets, including the IGF1R gene, at advanced metastatic stages. Paper-15107064. Here, we provide evidence that a naturally occurring nontoxic flavanoid, silibinin, targets the epidermal growth factor receptor ( EGFR), insulin-like growth factor-1 receptor ( IGF-1R) and NF-kappaB (nuclear factor-kappa B) pathways in PCA. Paper-12013377. We have shown previously that the extracellular sequences of the human insulin receptor ( IR) and the insulin-like growth factor I receptor ( IGFR) have an inhibitory effect on protein tyrosine kinase ( PTK) activity and on the biological functions of their respective Gag-receptor fusion proteins. Paper-7847266. Analysis of the ability of the full-length IGFR and its mutant receptors described above to associate with phosphatidylinositol 3 kinase indicated that the association required PTK activity and tyrosine phosphorylation of the receptors and correlated well with their transforming activities. Paper-7847266. In Sp1-null Drosophila Schneider cells, IGF1R promoter activity was dependent on exogenous Sp1, and was suppressed by full-length VHL protein ( pVHL) but only partially by truncated VHL lacking the Sp1- binding motif. pVHL also reduced the stability of IGF1R mRNA via sequestration of HuR protein. Paper-12515286. This two-hybrid system (the interaction trap) utilizes a hybrid protein containing the LexA DNA-binding domain fused to the intracellular portion of the IGF-I receptor (LexA- IGFIR beta) and hybrids containing an activation domain fused to either IRS-1 (Ad- IRS-1), Shc (Ad-Shc), or a cDNA library. Paper-781623. Using phosphopeptides corresponding to IGF-I receptor phosphorylation sites, we determined that the p85- and Syp- GST association with the IGF-I receptor could be inhibited by a carboxyl-terminal peptide containing pY1316 and that the GAP- GST association could be inhibited by a NPXY domain peptide. Paper-319693. However, because depletion of beta-arrestin 1 almost completely eliminated degradation, and IGF-1 induced down-regulation of the receptor in these cells, whereas beta-arrestin 2 only had a partial effect, beta-arrestin 1 seems to the more important isoform in affecting the expression of IGF-1R. Paper-10750133. Treatment of cells with the PI3K inhibitor LY294002 before release from stress resulted in a concentration-dependent loss of EGFR activation, whereas treatment with the MAPK inhibitor PD98059 did not block EGFR activation, indicating that EGFR activation was downstream of the IGF1R/ PI3K pathway. Paper-13018152. METHODS: A cohort of 1,665 adult, female mutation carriers, including 1,122 BRCA1 carriers (433 cases) and 543 BRCA2 carriers (238 cases) were genotyped for SNPs in IGF1, IGF1 receptor ( IGF1R), IGF1 binding protein ( IGFBP1, IGFBP2, IGFBP5), and IGF receptor substrate 1 ( IRS1). Paper-14613819. By polymerase chain reaction ( PCR) strategy, we obtained full-length 1123-bp GH, 817-bp IGF-I, 1584-bp TRbeta, and 2571-bp GR cDNAs, coding for 210 amino acid (aa) GH, 161 aa IGF-I, 378 aa TRbeta, and 745 aa GR putative proteins, and partial-length 158-bp GHR, 811-bp IGF-IR, and 446-bp TRalpha cDNAs. Paper-12373810. In GST- SOCS-3 pull-down experiments using IGFIR from mammalian cells and in immunoprecipitation experiments in which IGFIR and FLAG- SOCS-3 were transiently expressed in human embryonic kidney 293 cells, we found that SOCS-3 interacts constitutively with IGFIR in vitro and in intact cells. Paper-8612732. CONCLUSIONS: ER alpha is involved in the transient activation of ERK/ mitogen activated protein kinase ( MAPK) by genistein via its early association with IGF-IR, leading to hyper-responsiveness of LM cells and confirming that ER signaling is enhanced by activation of ERK/ MAPK in LM cells. Paper-12933785. Using the yeast two-hybrid system, a genetic assay for studying protein-protein interactions, we have examined and compared the interaction of the insulin-like growth factor-I receptor ( IGF-IR) and the insulin receptor ( IR) with their two known substrates p52Shc and the insulin receptor substrate-1 ( IRS-1). Paper-377093. Activation of insulin and IGF signaling pathways was studied by analysis of the phosphorylation status of IGF-IR and of key signaling proteins of the phosphoinositide 3-kinase (PI3K)/Akt and MAP kinase pathways, by the use of specific PI3K and MAP kinase inhibitors, and by silencing of IR and IGF-IR. Paper-14538352. We have investigated the molecular mechanism by which two growth factors, insulin-like growth factor-I (IGF-I) and basic fibroblast growth factor ( bFGF) regulate IGF-IR gene expression. bFGF increases the endogenous IGF-IR mRNA levels and IGF-IR promoter activity. Paper-932351. In this report we have replaced residues 260-277 of human IR with residues 253-266 of the human IGF-1R to produce an IR-based, cysteine loop exchange chimaera, termed hIR-Cys loop exchange (CLX), in which all 14 amino acid residues in the exchanged loop differ from wild-type insulin receptor. Paper-2156160. The results showed that the overall accuracy of survival prediction reached 92.3% for individual breast cancer patients with the use of the expression profiles of phospho- EGFR, phospho-ER, phospho- HER2/neu, phospho- IGFIR/In, phospho- MAPK, and phospho- p70S6K plus the selected clinical factors. Paper-12477604. In order to generate neural stem cells with increased ability to survive after transplantation in brain parenchyma we developed a chimeric receptor (ChR) that binds to myelin oligodendrocyte glycoprotein ( MOG) via its ectodomain and activates the insulin-like growth factor receptor type 1 ‎‎( IGF1R) signalling cascade. Paper-16034431. These results suggest that oxidative-stress-induced repression of IGF1R is mediated by the association of phosphorylated p53 with the IGF1R promoter via TBP, and by the subsequent recruitment of chromatin-modifying proteins, such as HDAC1, to the IGF1R promoter-TBP- p53 complex. Paper-13426491. Pretreatment of Chinese hamster ovary (CHO) cells overexpressing a human IR (CHO-HIR cells) with AG1024, an inhibitor for IR protein tyrosine kinase ( PTK) and IGF-1R- PTK, blocked Zn(2+)-induced ERK1/2 and PKB phosphorylation, but AG1478, an inhibitor for EGFR, was without effect in CHO cells. Paper-14185930. The beneficial effects of insulin were abrogated by insulin receptor (IR)/insulin-like growth factor receptor ( IGFR) or phosphoinositide-3 kinase ( PI3-K) blockade, suggesting that insulin- induced EC proliferation and viability are mediated through pIR/pIGFR and PI3-K effectors. Paper-13595933. Using normal human keratinocytes grown in vitro, we have demonstrated that activation of the IGF-1R promotes the premature senescence of UVB-irradiated keratinocytes through increased generation of reactive oxygen species (ROS) and by maintaining the expression of the cyclin-dependent kinase inhibitor p21(CDKN1A). Paper-14305836. The potential involvement of ATM in regulation of IGF-IR expression and function was investigated in isogenic cells with and without ATM function [AT22IJE-T/pEBS7 ( ATM -/-) and ATM-corrected AT22IJE-T/YZ5 ( ATM +/+) cells and 293 human embryonic kidney cells transfected with small interfering RNAs targeted to ATM]. Paper-10634510. Our results can be summarized as follows: (1) the activation of the IGF-1 receptor by its ligand, IGF-1, is an obligatory step in the proliferation of fibroblasts and hemopoietic cells; and (2) the expression of DNA synthesis genes, such as PCNA, DNA polymerase alpha, and cdc2, is dependent on the expression of previous genes. Paper-100457. To assess the potential functional interactions between BRCA1 and p53 in transcriptional control of the IGF-IR gene, co-transfections were performed on MCF-7 breast cancer cells using an IGF-IR promoter luciferase reporter construct together with expression vectors encoding BRCA1 and wild-type and mutant p53. Paper-10173619. We investigated this crosstalk under different conditions and found that both Akt and ERK activation induced by S1P, but not lysophosphatidic acid (LPA), in HEY ovarian cancer cells required PDGFR but not epidermal growth factor receptor ( EGFR) or insulin-like growth factor-I receptor ( IGFR). Paper-10207387. We identified two molecular aspects contributing to synergy: (a) inhibition of EGFR or IGF-IR individually promotes activation of the reciprocal receptor; (b) inhibition of EGFR-directed mitogen-activated protein kinase ( MAPK) shifts regulation of Akt from EGFR toward IGF-IR. Paper-13035955. Using MCF-7 breast cancer cells, we for the first time demonstrated that a sequential activation of IGF-IR, MMP, and EGFR existed in E2 and IGF-I actions, which was supported by evidence that the selective inhibitors of IGF-IR and MMP or knockdown of IGF-IR all inhibited E2- or IGF-I- induced EGFR phosphorylation. Paper-13343508. BACKGROUND: This study determined whether the resistance to the mitogenic effect of insulinlike growth factor 1 ( IGF-1) in AGS (we found that IGF-1 had almost no effect on the growth of AGS) cells is caused by the absence of IGF-1 receptor on the cells or by the interference of endogenous IGFs and IGF-binding protein ( IGFBP). Paper-91213. We treated A2780 ovarian cancer cells by weekly cycles of cisplatin over a period of 6 months and unveiled that enhanced insulin-like growth factor I receptor ( IGF-IR) expression and autocrine IGF-I are associated with hyperactivation of the IGF-IR and phosphatidylinositol-3-OH kinase ( PI3K) pathways in cisplatin-resistant cells. Paper-13697845. Immunohistochemical analyses were performed for EGFR, KIT, PDGFRA, somatostatin receptor subtypes 2A and 5 (SSTR5), vascular endothelial growth factor receptor 1, mammalian target of rapamycin (mTOR), insulin-like growth factor 1 receptor ( IGF1R), heat shock protein 90 (Hsp90), and transforming growth factor-beta receptor 1 ( TGFBR1). Paper-15186224. Our results demonstrate that IGF1R is downregulated by P53, and that siRNA targeting of IGF1R increases liver cancer cells sensitivity to adriamycin and promotes apoptosis. siRNA targeting of IGF1R could be potentially useful for increasing sensitivity to anti-cancer drugs, especially in drug-resistant cells with mutated P53. Paper-12454462. MATERIALS AND METHODS: Antibodies targeting epidermal growth factor receptor ( EGFR) (cetuximab), insulin-like growth factor-1 receptor ( IGF-IR) (IMC-A12) or vascular endothelial growth factor receptor 2 ( VEGFR2) (DC101), were dosed alone or in combination, in 11 human tumor xenograft models established in mice. Paper-13840465. We concluded that p53mt249 stimulates IGF-II dependent IGF-IR signaling by upregulating the expression of both ligand ( IGF-II) and receptor ( IGF-IR) through an autocrine and/or paracrine loop and we outline the physiological significance of potentiation of IGF-IR by p53 mutation in the development of hepatocellular carcinoma ( HCC). Paper-9930201. This study evaluated the expression profile of hepatocyte growth factor ( HGF), c-Met, epidermal growth factor receptor ( EGFR), insulin-like growth factor-1 receptor ( IGF-1R), and vitreal and serum EGF, HGF, IGF-1 levels in patients with uveal melanoma and assessed their correlation with the clinicopathological parameters. Paper-14274500. Sequence analysis of the IGF1 and IGF1 receptor ( IGF1R) genes of female centenarians showed overrepresentation of heterozygous mutations in the IGF1R gene among centenarians relative to controls that are associated with high serum IGFI levels and reduced activity of the IGFIR as measured in transformed lymphocytes. Paper-14290744. In this study, we show that decorin promotes alpha2beta1 integrin-dependent endothelial cell adhesion and migration on fibrillar collagen type I. We provide evidence that decorin modulates cell-matrix interaction in this context by stimulating cytoskeletal and focal adhesion reorganization through activation of the IGF-IR and the small GTPase Rac. Paper-12832363. In CHO cells stably increasing V922E IGF-IR, both IRS-1 phosphorylation and the IRS-1 associated phosphoinositide 3-kinase activity were stimulated in the absence of IGF-I to the level attained by 1 nM IGF-I stimulation of wild-type IGF-IR, whereas the Ras-mitogen-activated protein kinase pathway was not activated under the same condition. Paper-319684. Clinicopathological significance of the gene expression of matrix metalloproteinase-7, insulin-like growth factor-1, insulin-like growth factor-2 and insulin-like growth factor-1 receptor in patients with colorectal cancer: insulin-like growth factor-1 receptor gene expression is a useful predictor of liver metastasis from colorectal cancer. Paper-12934038. PTEN knockdown increased basal and ligand-induced activation of the insulin-like growth factor-I (IGF-I) and ErbB3 receptor tyrosine kinases, and prolonged the association of the p85 PI3K subunit with the IGF-I receptor ( IGF-IR) effector insulin receptor substrate-1 and with ErbB3, implicating PTEN in the modulation of signaling upstream of PI3K. Paper-13774361. Mechanistically, we find that inhibition of the MAPK pathway circumvents a negative feedback loop imposed on the IGF-IR- insulin receptor substrate 1 ( IRS-1) signaling complex, a molecular scenario that parallels the negative feedback loop between mTOR-p70S6K and IRS-1 that mediates rapamycin-directed IGF-IR signaling. Paper-13035955. The c-Met ribozyme inhibited IGF-I- and HGF-mediated migration and invasion, indicating that c-Met is essential for these processes. uPA and uPAR inhibition blocked IGF-I- and HGF-mediated migration and invasion, suggesting that uPAR is downstream of IGF/ IGF-IR and HGF/ c-Met in the signaling pathways that mediate cell migration and invasion. Paper-10777532. The expression of p- mTOR, VEGF, cleaved caspase 3 ( CC3), proliferating cell nuclear antigen ( PCNA), IGF1, IGF1R, phosphorylated extracellular signal-regulated kinase, p-P70S6K, HIF1alpha, and VEGF in LCE, LCECs, and wild-type cholangiocytes was studied with immunohistochemistry, western blotting, or enzyme-linked immunosorbent assays. Paper-15076591. These synonyms are used for gene IGF1R (insulin-like growth factor 1 receptor): MGC18216, MGC142172, MGC142170, JTK13, Insulin-like growth factor I receptor, Insulin-like growth factor 1 receptor, IGFR, IGF-I receptor, IGFIR, CD221. These accession numbers are used for gene IGF1R: Q14CV2 (UNIPROT__AC), EU826611 (NCBI_GENBANK__AC), BC113612 (NCBI_GENBANK__AC), B1B5Y2 (UNIPROT__AC). IGF1R is a homologue of INR (insulin receptor (AGAP012424-PA)) from Anopheles gambiae str. PEST. IGF1R is a homologue of InR (Insulin-like receptor) from Drosophila melanogaster. IGF1R is a homologue of igf1rb (insulin-like growth factor 1b receptor) from Danio rerio. IGF1R is a homologue of igf1ra (insulin-like growth factor 1a receptor) from Danio rerio. IGF1R is a homologue of IGF1R (insulin-like growth factor 1 receptor) from Pan troglodytes. IGF1R is a homologue of IGF1R (insulin-like growth factor 1 receptor) from Canis lupus familiaris. IGF1R is a homologue of IGF1R (insulin-like growth factor 1 receptor) from Bos taurus. IGF1R is a homologue of IGF1R (insulin-like growth factor 1 receptor) from Gallus gallus. IGF1R is a homologue of Igf1r (insulin-like growth factor I receptor) from Mus musculus. IGF1R is a homologue of Igf1r (insulin-like growth factor 1 receptor) from Rattus norvegicus. IGF1R is a homologue of daf-2 (abnormal DAuer Formation) from Caenorhabditis elegans. Important links ! iHOP - Information Hyperlinked over Proteins . Concept & Implementation by Robert Hoffmann.