Functional Analysis of Breast Cancer Susceptibility Gene BRCA2.
Abstract
In order to study the physiological function and the mechanism by which the breast cancer susceptibility gene BRCA2 is involved in breast cancer, I have generated and characterized a series of polyclonal and monoclonal antibodies against BRCA2. By using these antibodies, I demonstrated that the BRCA2 gene product is a 460-kDa nuclear phosphoprotein, and that abnormality in its distribution does not seem to be the mechanism by which it is involved in tumorigenesis. I also found that BRCA2 forms in vivo complexes with both p53 and RAD51. Moreover, exogenous BRCA2 expression in cancer cells inhibits p53's transcriptional activity, and RAD51 co-expression enhances BRCA2's inhibitory effects. These findings demonstrate that BRCA2 physically and functionally interacts with two key components of cell cycle control and DNA repair pathways. Thus, BRCA2 likely participates with p53 and RAD51 1 in maintaining genome integrity. The major goals of this study are to provide a basis for designing agents that could regulate BRCA2's production or replace its function by the molecular dissection of its functional pathways, and to identify components of the signaling pathway of BRCA2 that may be used as novel biomarkers for breast tumor prognosis, with the goal of developing effective intervention protocols.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 1998
- Accession Number
- ADA365459
Entities
People
- Lihua Y. Marmorstein
Organizations
- Icahn School of Medicine at Mount Sinai