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The BRCA1 185delAG truncation protein (BRAt) has been shown to increase caspase-mediated apoptosis in normal human ovarian surface epithelial (HOSE) cells and ovarian cancer cells. Previous studies in our lab demonstrated that members of the IAP family are downregulated in BRAt cells. Interestingly, the mammary serine protease inhibitor, maspin, has been shown to sensitize breast carcinoma cells by decreasing IAP protein expression, similar to BRAt. We hypothesized that BRAt protein expression induces maspin protein expression in ovarian surface epithelial cells. Maspin protein levels in normal HOSE cells that are heterozygous carriers of the BRCA1 185delAG mutation were compared to other normal HOSE cells with homozygous full-length BRCA1. All four BRCA1 185delAG mutation carriers tested showed higher maspin levels than six of seven full-length BRCA1 cell lines. Normal HOSE BRCA1 wild-type cells were transfected with BRAt protein and showed increased maspin mRNA levels and increased maspin protein levels as compared to mock-transfected cells. Studies are currently under way to further elucidate the relationship between BRAt and maspin protein expression and their apoptotic effects. A better understanding of the chemosensitizing properties that these two proteins share might lead to more effective adjuvant therapy for the management of drug-resistant cancers.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA