Abstract
Abstract : BRCA1 is a tumor suppressor gene for hereditary breast and ovarian cancers. In collaborating with various binding partners, BRCA1 protein participates in multiple cellular functions. Characterization of these binding proteins of BRCA1 is therefore key to the complete understanding of BRCA1's role in tumor suppression. Cofactor of BRCA1 (COBRA1)is a novel BRCA1- interacting protein identified in our laboratory. Subsequent work suggests that COBRA1 and BRCA1 share several functional commonalities in regulating high-order chromatin structure and estrogen-dependent gene expression. During the past year, we made significant progress in elucidating the role of COBRA1 in breast cancers. By analyzing COBRA1 expression in breast cancer clinical samples, we found that COBRA1 level was inversely correlated with breast cancer progression. Concordantly, depletion of COBRA1 in breast cancer cells led to elevated cell growth under suboptimal concentrations of estrogen both in vivo and in vitro. Thus, our work uncovered an important role of COBRA1 in breast cancer. It also provides a solid and logical foundation for exploring a synergistic relationship between BRCA1 and COBRA1 in the next phase of the funded study.
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