Estrogen and Retinoid Regulation of DNA Repair in Breast Cancer
Abstract
BRCA1 is involved in repair of double strand breaks induced by ionizing radiation and chemotherapy drugs. BRCA1 and nuclear hormone receptors interact with p3OO and CREB binding protein (CBP) to activate target gene transcription. Few studies have suggested a role for nuclear hormone receptors in DNA repair. E2 and RA had opposing effects on DNA damage and breast cancer cell survival following double strand break damage. Estradiol but not retinoic acid treatment resulted in complex formation between ERalpha, CBP, and BRCA1 in ER positive breast cancer cell lines. Mutant BRCA1 reduced DNA damage repair protein expression in human breast cancer cell lines. Mutant BRCA1 expression correlated with increased DNA damage and decreased repair activity in breast cancer cell lines but did not block nuclear hormone dependent effects. The truncated BRCA1 failed to form complexes with ERalpha and CBP which correlated with its ability to exert E2 independent effects on DNA repair. Mutant BRCA1 produced increased survival in breast cancer cells with DNA double strand breaks and inhibited cell cycle progression. Ectopic ERalpha expression was sufficient to produce the E2 mediated effects on DNA damage, repair, and survival.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2005
- Accession Number
- ADA435641
Entities
People
- David L Crowe
Organizations
- University of Southern California