Consequences of Cyclin D1/BRCA1 Interaction in Breast Cancer Progression
Abstract
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 ofcyclin D1/BRCA1 binding in breast cancer cells. Therefore, I hypothesize that the direct interaction ofcyclin Di with ERCA1 results in the cell cycle dependent regulation of the activity ofBRCAi. In this study, I wish to identiy and confirm the cell cycle dependent cyclin D1/BRCA1 interaction in breast cancer cells, determine the biochemical consequence of cyclin D1/BRCAi interaction in breast cancer cells, and determine the flinctional consequence of BRCA1 phosphorylation in breast cancer. BRCA1's phosphorylation by cyclin D1/cdk 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 BRCA15 ability to bind DNA, either as a transcription factor or as part ofaDNA damage repair complex. Determining the consequences of the interaction of cyclin D1/BRCA1 could lead to a more complete understanding of how breast cancer occurs, thus leading to new treatment options.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2005
- Accession Number
- ADA437241
Entities
People
- Fatab Kashanchi
- Kylene Kehn
- Maria E. Bottazzi
Organizations
- George Washington University