Estrogen and Retinoid Regulation of DNA Repair in Breast Cancer
Abstract
Breast cancer is one of the leading causes of death in women. BRCAl has an important role in DNA repair. Chemotherapeutic agents used in the treatment of breast cancer produce their cytotoxic effects by creating DNA damage. Estrogen (ER) and retinoid acid receptors (RAR) are members of a family of ligand dependent transcription factors. ER, RAT, and BRCA require CREB binding protein (CVP) to activate target gene transcription. The application proposed a new mechanism by which ER and RAR regulate BRCA1 mediated DNA repair via CBP. In the first year of the project, we determined that CBP is recruited to ligand bound ER and RAR in breast cancer cells. This recruitment is accompanied by decreased association of CBP with BRCAl. E2 and RA treatment of human breast cancer cell lines did not directly alter expression of DNA repair proteins with the exception of MsH2. We determined that RA increased apoptosis induced by etoposide, but that E2 protected ER+ breast cancer cells against apoptosis induced by etoposide alone or the combination of etoposide and RA. E2 failed to protect ER+ cells from cisplatin induced apoptosis, and treatment with the E2/RA combination resulted in the highest levels of cisplatin induced apoptosis.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2003
- Accession Number
- ADA417054
Entities
People
- David L Crowe
Organizations
- University of Southern California