Functional insulin receptors on human epithelial ovarian carcinoma cells: implications for IGF-II mitogenic signaling.
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 (125)I-insulin binding and mitogenic responses to insulin. All cancer cell and OSE cultures specifically bound (125)I-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 (3)H-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 (125)I-insulin binding. Direct binding of (125)I-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.
Kalli
Kimberly R
KR
Division of Endocrinology and Metabolism, Endocrine Research Unit, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Falowo
Oluwole I
OI
Bale
Laurie K
LK
Zschunke
Michael A
MA
Roche
Patrick C
PC
Conover
Cheryl A
CA
D017398:Alternative Splicing; D002455:Cell Division; D003432:Cross-Linking Reagents; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011972:Receptor, Insulin / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D003432:Cross-Linking Reagents; D007328:Insulin; D007457:Iodine Radioisotopes; D020033:Protein Isoforms; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin