This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kalli, K. R. Articles by Conover, C. A. Search for Related Content PubMed PubMed Citation Articles by Kalli, K. R. Articles by Conover, C. A. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Medline Plus Health Information Ovarian Cancer

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

Division of Endocrinology and Metabolism, Endocrine Research Unit (K.R.K., O.I.F., L.K.B., C.A.C.) and Division of Experimental Pathology (M.A.Z., P.C.R.), Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Dr. Cheryl Conover, Endocrine Research Unit, Mayo Clinic, 200 First Street Southwest, 5-194 Joseph, Rochester, Minnesota 55905. E-mail: conover.cheryl{at}mayo.edu.

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.

This article has been cited by other articles:

				P. D. Ryan and P. E. Goss The Emerging Role of the Insulin-Like Growth Factor Pathway as a Therapeutic Target in Cancer Oncologist, January 1, 2008; 13(1): 16 - 24. [Abstract] [Full Text] [PDF]

				P. Haluska, H. M. Shaw, G. N. Batzel, D. Yin, J. R. Molina, L. R. Molife, T. A. Yap, M. L. Roberts, A. Sharma, A. Gualberto, et al. Phase I Dose Escalation Study of the Anti Insulin-Like Growth Factor-I Receptor Monoclonal Antibody CP-751,871 in Patients with Refractory Solid Tumors Clin. Cancer Res., October 1, 2007; 13(19): 5834 - 5840. [Abstract] [Full Text] [PDF]

				D. Spentzos, S. A Cannistra, F. Grall, D. A Levine, K. Pillay, T. A Libermann, and C. S Mantzoros IGF axis gene expression patterns are prognostic of survival in epithelial ovarian cancer Endocr. Relat. Cancer, September 1, 2007; 14(3): 781 - 790. [Abstract] [Full Text] [PDF]

				Q.-s. Ji, M. J. Mulvihill, M. Rosenfeld-Franklin, A. Cooke, L. Feng, G. Mak, M. O'Connor, Y. Yao, C. Pirritt, E. Buck, et al. A novel, potent, and selective insulin-like growth factor-I receptor kinase inhibitor blocks insulin-like growth factor-I receptor signaling in vitro and inhibits insulin-like growth factor-I receptor dependent tumor growth in vivo Mol. Cancer Ther., August 1, 2007; 6(8): 2158 - 2167. [Abstract] [Full Text] [PDF]

				A. A. Samani, S. Yakar, D. LeRoith, and P. Brodt The Role of the IGF System in Cancer Growth and Metastasis: Overview and Recent Insights Endocr. Rev., February 1, 2007; 28(1): 20 - 47. [Abstract] [Full Text] [PDF]

				B. Davidson, Z. Zhang, L. Kleinberg, M. Li, V. A. Florenes, T.-L. Wang, and I.-M. Shih Gene expression signatures differentiate ovarian/peritoneal serous carcinoma from diffuse malignant peritoneal mesothelioma. Clin. Cancer Res., October 15, 2006; 12(20): 5944 - 5950. [Abstract] [Full Text] [PDF]

				L. Lu, D. Katsaros, A. Wiley, I. A. Rigault de la Longrais, H. A. Risch, M. Puopolo, and H. Yu The Relationship of Insulin-Like Growth Factor-II, Insulin-Like Growth Factor Binding Protein-3, and Estrogen Receptor-{alpha} Expression to Disease Progression in Epithelial Ovarian Cancer Clin. Cancer Res., February 15, 2006; 12(4): 1208 - 1214. [Abstract] [Full Text] [PDF]

				A. Denley, G. V. Brierley, J. M. Carroll, A. Lindenberg, G. W. Booker, L. J. Cosgrove, J. C. Wallace, B. E. Forbes, and C. T. Roberts Jr. Differential Activation of Insulin Receptor Isoforms by Insulin-Like Growth Factors Is Determined by the C Domain Endocrinology, February 1, 2006; 147(2): 1029 - 1036. [Abstract] [Full Text] [PDF]

				P. Haluska, J. M. Carboni, D. A. Loegering, F. Y. Lee, M. Wittman, M. G. Saulnier, D. B. Frennesson, K. R. Kalli, C. A. Conover, R. M. Attar, et al. In vitro and In vivo Antitumor Effects of the Dual Insulin-Like Growth Factor-I/Insulin Receptor Inhibitor, BMS-554417 Cancer Res., January 1, 2006; 66(1): 362 - 371. [Abstract] [Full Text] [PDF]

				A. Denley, E. R. Bonython, G. W. Booker, L. J. Cosgrove, B. E. Forbes, C. W. Ward, and J. C. Wallace Structural Determinants for High-Affinity Binding of Insulin-Like Growth Factor II to Insulin Receptor (IR)-A, the Exon 11 Minus Isoform of the IR Mol. Endocrinol., October 1, 2004; 18(10): 2502 - 2512. [Abstract] [Full Text] [PDF]

				J. L. Phy, C. A. Conover, D. H. Abbott, M. A. Zschunke, D. L. Walker, D. R. Session, I. S. Tummon, A. R. Thornhill, T. G. Lesnick, and D. A. Dumesic Insulin and Messenger Ribonucleic Acid Expression of Insulin Receptor Isoforms in Ovarian Follicles from Nonhirsute Ovulatory Women and Polycystic Ovary Syndrome Patients J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3561 - 3566. [Abstract] [Full Text] [PDF]

				M. Laudes, C. Christodoulides, C. Sewter, J. J. Rochford, R. V. Considine, J. K. Sethi, A. Vidal-Puig, and S. O'Rahilly Role of the POZ Zinc Finger Transcription Factor FBI-1 in Human and Murine Adipogenesis J. Biol. Chem., March 19, 2004; 279(12): 11711 - 11718. [Abstract] [Full Text] [PDF]

				G. Pandini, E. Medico, E. Conte, L. Sciacca, R. Vigneri, and A. Belfiore Differential Gene Expression Induced by Insulin and Insulin-like Growth Factor-II through the Insulin Receptor Isoform A J. Biol. Chem., October 24, 2003; 278(43): 42178 - 42189. [Abstract] [Full Text] [PDF]

				L. Sciacca, M. Prisco, A. Wu, A. Belfiore, R. Vigneri, and R. Baserga Signaling Differences from the A and B Isoforms of the Insulin Receptor (IR) in 32D Cells in the Presence or Absence of IR Substrate-1 Endocrinology, June 1, 2003; 144(6): 2650 - 2658. [Abstract] [Full Text] [PDF]

				R. J. Walsh, T. Reinot, J. M. Hayes, K. R. Kalli, L. C. Hartmann, and G. J. Small Carcinoma and SV40-Transfected Normal Ovarian Surface Epithelial Cell Comparison by Nonphotochemical Hole Burning Biophys. J., February 1, 2003; 84(2): 1299 - 1307. [Abstract] [Full Text] [PDF]