Insulin‐like growth factor ligands, receptors, and binding proteins in cancer

Foulstone, Emily J.; Prince, SN; Zaccheo, OJ; Burns, JL; Harper, James M.; Jacobs, CI; Church, David N.; Hassan, A. Bassim

doi:10.1002/path.1712

Cited by 228 publications

(192 citation statements)

References 71 publications

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“…Moreover, binding of the growth factor receptor-bound protein 2 (Grb2) leads to the activation of the Raf/ mitogen-activated protein kinase family (MAPK) signaling pathway. Together, this regulatory network results in the transcriptional activation of numerous target genes including p27 kip1 , MYC, FOS, cyclin B and Vascular Endothelial Growth Factor (VEGF); (reviewed by Foulstone et al, 2005).…”

Section: Signaling Pathways and Their Dysregulationmentioning

confidence: 99%

Dysregulation of growth factor signaling in human hepatocellular carcinoma

2006

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Section: Signaling Pathways and Their Dysregulationmentioning

confidence: 99%

Dysregulation of growth factor signaling in human hepatocellular carcinoma

2006

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“…IGF2 binds to the IGF-I receptor to initiate intracellular signaling cascades that lead to cell proliferation (5,6). Increased expression of IGF2 is a common feature of both pediatric and adult malignancies (5), and mounting evidence implicates IGF2 as a major factor contributing to oncogenesis.…”

Section: Introductionmentioning

confidence: 99%

Frequent IGF2/H19 Domain Epigenetic Alterations and Elevated IGF2 Expression in Epithelial Ovarian Cancer

Murphy

Huang

Wen

et al. 2006

Molecular Cancer Research

125

103

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Overexpression of the imprinted insulin-like growth factor-II (IGF2) is a prominent characteristic of gynecologic malignancies. The purpose of this study was to determine whether IGF2 loss of imprinting (LOI), aberrant H19 expression, and/or epigenetic deregulation of the IGF2/H19 imprinted domain contributes to elevated IGF2 expression in serous epithelial ovarian tumors. IGF2 LOI was observed in 5 of 23 informative serous epithelial ovarian cancers, but this did not correlate with elevated expression of IGF2 H19 RNA expression levels were also found not to correlate with IGF2 transcript levels. However, we identified positive correlations between elevated IGF2 expression and hypermethylation of CCCTC transcription factor binding sites 1 and 6 at the H19 proximal imprint center (P = 0.05 and 0.02, respectively). Hypermethylation of CCCTC transcription factor sites 1 and 6 was observed more frequently in cancer DNA compared with lymphocyte DNA obtained from women without malignancy (P < 0.0001 for both sites 1 and 6). Ovarian cancers were also more likely to exhibit maternal allele-specific hypomethylation upstream of the imprinted IGF2 promoters when compared with normal lymphocyte DNA (P = 0.004). This is the same region shown previously to be hypomethylated in colon cancers with IGF2 LOI, but this was not associated with LOI in ovarian cancers. Elevated IGF2 expression is a frequent event in serous ovarian cancer and this occurs in the absence of IGF2 LOI. These data indicate that the epigenetic changes observed in these cancers at the imprint center may contribute to IGF2 overexpression in a novel mechanistic manner. (Mol Cancer Res 2006;4(4):283 -92)

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“…Dysregulation of the IGF-I system has been implicated in the proliferation of numerous neoplasms (2,11). Elevation of serum IGF-I increases the risk of developing several cancers, including colon (9), and IGF-IR is also important for tumor maintenance (12,13).…”

Section: Introductionmentioning

confidence: 99%

Insulin-like growth factor-I receptor blockade by a specific tyrosine kinase inhibitor for human gastrointestinal carcinomas

Piao

Wang

Adachi

et al. 2008

Molecular Cancer Therapeutics

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Insulin-like growth factor-I receptor (IGF-IR) signaling is required for carcinogenicity and proliferation of gastrointestinal (GI) cancers. In this study, we sought to evaluate the effect of a new tyrosine kinase inhibitor of IGF-IR, NVP-AEW541, on the signal transduction and the progression of GI carcinomas. We assessed the effect of NVP-AEW541 on signal transduction, proliferation, survival, and migration in four GI cancer cells: colorectal adenocarcinoma HT29, pancreatic adenocarcinoma BxPC3, esophageal squamous cell carcinoma TE1, and hepatoma PLC/PRF/5. The effects of NVP-AEW541 alone and with chemotherapy were studied in vitro and in nude mouse xenografts. We also analyzed the effects of NVP-AEW541 on insulin signals and hybrid receptor formation between IGF-IR and insulin receptor. NVP-AEW541 blocked autophosphorylation of IGF-IR and both Akt and extracellular signal-regulated kinase activation by IGF but not by insulin. NVP-AEW541 suppressed proliferation and tumorigenicity in vitro in a dose-dependent manner in all cell lines. The drug inhibited tumor as a single agent and, when combined with stressors, up-regulated apoptosis in a dose-dependent fashion and inhibited mobility. NVP-AEW541 augmented the effects of chemotherapy on in vitro growth and induction of apoptosis. Moreover, the combination of NVP-AEW541 and chemotherapy was highly effective against tumors in mice. This compound did not influence hybrid receptor formation. Thus, NVP-AEW541 may have significant therapeutic utility in human GI carcinomas both alone and in combination with chemotherapy. [Mol Cancer Ther 2008;7(6):1483 -93]

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Insulin‐like growth factor ligands, receptors, and binding proteins in cancer

Cited by 228 publications

References 71 publications

Dysregulation of growth factor signaling in human hepatocellular carcinoma

Dysregulation of growth factor signaling in human hepatocellular carcinoma

Frequent IGF2/H19 Domain Epigenetic Alterations and Elevated IGF2 Expression in Epithelial Ovarian Cancer

Insulin-like growth factor-I receptor blockade by a specific tyrosine kinase inhibitor for human gastrointestinal carcinomas

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