Regulation of BRCA1 Transcription by Specific Single-Stranded DNA Binding Factors

Abstract

Since the majority of high-grade breast cancers express reduced levels of BRCA1 mRNA, we investigated the factors regulating BRCA1 transcription. Factors with specific affinity for the previously identified positive regulatory region (PRR) in the BRCA1 promoter were purified from whole-cell extracts. Identified proteins included replication protein A and a series of related factors with affinity for the sense strand of PRR. A subset of the identified factors activated the BRCA1 promoter. Identification of these families of proteins regulating the BRCA1 promoter represents an important step in the comprehension of the mechanisms responsible for breast cancer development.

ACKNOWLEDGMENTS

This study was supported by program project grants 5P30CA56036 (Translational Research in Cancer) and 5PO1CA76259 (Oncogene Deregulation) from U.S. Public Health Sciences to Carlo M. Croce and by Department of Defense breast cancer fellowship DAMD17-98-1-8170 to Sanjay Thakur.

We thank Arnold B. Rabson for critical reading of the manuscript and helpful suggestions. We also thank Richard Fishel, Marc Wold for RPA cDNA clones, David Levens for FBP-1 reagents, and Maria F. Czyzyk-Krzeska for PCBP-1 antibody. We are also grateful to Devjani Chatterjee at the KCI computing facility for computer-assisted analysis of the sequences of the purified factors.