Ovarian cancer is one of the deadliest forms of cancer. Very little is known about the factors that contribute to ovarian cancer formation and progression. A potential tumor suppressor gene that is located at 17p13, OVCA1, has been cloned. Expression of OVCA1 is reduce in ovarian tumor tissue as compared to normal ovarian epithelia, and over-expression of OVCA1 inhibits the proliferation of ovarian cancer cell lines. The goal of the research proposal is to determine how OVCA1 inhibits cellular proliferation, what role OVCA1 might play in normal biochemistry, and how loss or reduction of OVCA1 contributes to ovarian cancer formation and progression. Tissue culture models will be the primary resource for studying OVCA1. One aspect of the project will be to study how endogenous expression of OVCA1 is regulated in tumor cells grown in culture. The expression of OVCA will be examined by Western and Northern blotting under different hormonal conditions and in different phases of growth. Another part of the project will be to over-express OVCA1 and examine how the cell cycle is altered in response. Systems that allow induction of OVCA in response to addition of tetracycline or ecdysone analogs are being developed to aid these experiments. Initial experiments suggest that OVCA1 may block progression through G1 by indirectly lowering cyclin D levels. Biochemical pathways known to regulate D levels will be monitored as OVCA expression is induced. In addition, proteins that might interact with OVCA will be identified using yeast two-hybrid, farwestern, and co- immunoprecipitation techniques.
