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Kimberly Kalli, Ph.D.
Mayo Clinic and Foundation
Functional Significance of Insulin Receptors in Epithelial Ovarian Cancer: Therapeutic Implications
Project Summary
Ovarian cancer cells grow in response to a variety of growth factors. If proteins that allow a response to a specific growth factor exist on cancer cells but not on normal ovarian epithelial cells, it is possible that these proteins, called receptors, could serve as tumor-specific targets for new therapeutics. Recently, breast cancer cells were shown to have a version of the receptor for insulin that is different from the metabolically critical insulin receptor. This unique protein, called insulin receptor isoform A, primarily regulates cell growth instead of metabolism. Additionally, unlike the metabolic insulin receptor, isoform A can respond to insulin-like growth factor-II (IGF-II) as well as to insulin. Because IGF-II may be elevated locally in ovarian tumors, it is possible that IGF-II uses isoform A to control ovarian cancer cell growth.
My laboratory has shown that ovarian cancer cell lines have insulin receptors that control growth. The experiments outlined in my research proposal will use these cell lines and patient samples to determine the role of the insulin receptor in regulating ovarian cancer growth and tumorigenicity. They will: 1) characterize patient samples for expression of proteins that could contribute to insulin receptor-mediated effects; 2) show IGF-II-induced changes in cancer cell line activities in the laboratory; and 3) determine whether the availability of IGF-II changes the growth of ovarian cancer cells in animal models in a way correlated to the amount of insulin receptor isoform A that the cells express. These results will lead to a better fundamental understanding of the biology of ovarian cancer. Additionally, they may identify potential targets for therapeutics that would block the activation of insulin receptor isoform A while sparing the metabolic insulin receptor.
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