Functional Insulin Receptors on Human Epithelial Ovarian Carcinoma Cells: Implications for IGF-II Mitogenic Signaling

• Published in: Endocrinology (Philadelphia) 2002-09, Vol.143 (9), p.3259-3267
• Main Authors: Kalli, Kimberly R, Falowo, Oluwole I, Bale, Laurie K, Zschunke, Michael A, Roche, Patrick C, Conover, Cheryl A
• Format: Article
• Language: English
• Subjects: Alternative Splicing; Beta cells; Binding; Cancer; Cell Division; Cell number; Cell proliferation; Cross-Linking Reagents; Crosslinking; Electrophoresis, Polyacrylamide Gel; Epithelial Cells - metabolism; Epithelial Cells - pathology; Female; Flow Cytometry; Gene Expression; Humans; Immunoprecipitation; Insulin; Insulin - metabolism; Insulin - pharmacology; Insulin receptors; Insulin-Like Growth Factor I - metabolism; Insulin-like growth factor II; Insulin-Like Growth Factor II - pharmacology; Iodine Radioisotopes; Life span; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Polymerase Chain Reaction; Protein Isoforms - analysis; Protein Isoforms - genetics; Receptor mechanisms; Receptor, IGF Type 1 - metabolism; Receptor, Insulin - analysis; Receptor, Insulin - genetics; Receptor, Insulin - physiology; Receptors; RNA, Messenger - analysis; Signal Transduction; Thymidine; Transformed cells; Tumor cell lines; Tumor Cells, Cultured
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2001-211408

The insulin receptor mediates a proliferative response in certain transformed cells, but little is known about its function in ovarian cancer. We used human epithelial ovarian carcinoma cell lines and lifespan-extended normal ovarian surface epithelial (OSE) cells to examine 125I-insulin binding and mitogenic responses to insulin. All cancer cell and OSE cultures specifically bound 125I-insulin. Except for OV202, the carcinoma lines had elevated insulin binding compared with OSE cells. All carcinoma lines except OV202 expressed insulin receptor as detected by flow cytometry and increased 3H-thymidine incorporation or cell number in response to 0.1–10 nm insulin. Interestingly, similar concentrations of IGF-II also induced proliferation of the insulin-responsive cancer cell lines and displaced 125I-insulin binding. Direct binding of 125I-IGF-II to the insulin receptor was visualized by cross-linking and immunoprecipitation. Binding of IGF-II to the insulin receptor and a proliferative effect of insulin suggest the presence of insulin receptor isoform A. Real-time PCR analyses confirm that insulin receptor isoform A expression predominates over isoform B expression in the ovarian carcinoma cell lines. This report suggests that the insulin receptor may play a role in the regulation of ovarian cancer cell growth.