Characterization of BRCA2 Transcriptional Regulation
Abstract
The purpose of this award was to study the transcriptional regulation of the BRCA2 breast cancer predisposition gene with the goal of identifying agents capable of modulating BRCA2 expression. In this project we aimed to test the effect of a variety of transcription factors, hormones, and environmental agents on BRCA2 expression and to define regions within the promoter that are responsive to these and other agents. In the course of this study we have determined that the USE binding site in the minimal promoter regulates basal expression of BRCA2. In addition we have demonstrated that the NF kappa E transcription factor can induce the BRCA2 promoter. In contrast, we found that adriamycin (ADS) treatment down-regulates the BRCA2 promoter 10 fold in a p53 dependent manner and that this effect is associated with inhibition of USE binding to the promoter. ADS and wildtype p53 also reduce BRCA2 protein levels but do not influence the rate of BRCA2 degradation. The promoter studies have also determined that mitomycin C but not other DNA damaging agents influences the BRCA2 promoter. No other agents were found to have a significant effect on promoter activity suggesting that BRCA2 transcription is tightly regulated.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2001
- Accession Number
- ADB282112
Entities
People
- Fergus J. Couch