Consequences of Cyclin D1/BRCA1 Interaction in Breast Cancer Progression
Annual summary rept. 21 Mar 2003-20 Mar 2006
GEORGE WASHINGTON UNIV WASHINGTON DC
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The inheritance of one defective BRCA1 or BRCA2 allele predisposes an individual to developing breast, ovarian and T-cell cancers. In addition, in breast cancers where BRCA1 is not mutated, it is often functionally inactivated. Furthermore, cyclin D1 has been shown to be overexpressed in many cancers including breast cancer and its associates with BRCA1. Because of the crucial role of both of these proteins in cancer, it is reasonable to expect that this interaction has a significant role in tumor cells. The understanding of when this interaction occurs during cell cycle progression will help to determine the role of cyclin D1BRCA1 binding in breast cancer cells. Therefore, I hypothesize that the direct interaction of cyclin D1 with BRCA1 results in the cell cycle dependent regulation of the activity of BRCA1. In this study, I wish to identify and confirm the cell cycle dependent cyclin D1BRCA1 interaction in breast cancer cells, determine the biochemical consequence of cyclin D1BRCA1 interaction in breast cancer cells, and determine the functional consequence of BRCA1 phosphorylation in breast cancer. BRCA1s phosphorylation by cyclin D1cdk complexes may help to regulate BRCA1 s localization to the nucleus, since BRCA1 has been shown to have a cytoplasmic expression pattern, but acts primarily in the nucleus. Phosphorylation may also be important in modulating BRCA1s ability to bind DNA, either as a transcription factor or as part of a DNA damage repair complex. Determining the consequences of the interaction of cyclin D1BRCA1 could lead to a more complete understanding of how breast cancer occurs, thus leading to new treatment options.
- Anatomy and Physiology
- Medicine and Medical Research