Consequences of Cyclin D1/BRCA1 Interaction in Breast Cancer Progression
Abstract
The inheritance of one defective BRCAl or BRCA2 allele predisposes an individual to developing breast, ovarian and T-cell cancers. In addition, in breast cancers where BRCAl is not mutated, it is often functionally inactivated. Furthermore, cyclin Dl has been shown to be overexpressed in many cancers including breast cancer and its associates with BRCAl. 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 Dl/BRCAl binding in breast cancer cells. Therefore, I hypothesize that the direct interaction of cyclin Dl with BRCAl results in the cell cycle dependent regulation of the activity of BRCAl. In this study, I wish to identity and confirm the cell cycle dependent cyclin Dl/BRCAl interaction in breast cancer cells, determine the biochemical consequence of cyclin Dl/BRCAl interaction in breast cancer cells, and determine the functional consequence of BRCAl phosphorylation in breast cancer. BRCAl s phosphorylation by cyclin Dl/cdk complexes may help to regulate BRCAl's localization to the nucleus, since BRCAl has been shown to have a cytoplasmic expression pattern, but acts primarily in the nucleus. Phosphorylation may also be important in modulating BRCAl'1 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 Dl/BRCAl 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, 2004
- Accession Number
- ADA424028
Entities
People
- Fatah Kashanchi
- Kylene Kehn
Organizations
- George Washington University