Positive regulation of the BRCA1 promoter

Inherited mutations in the BRCA1 gene, presumably leading to loss of functi on, confer susceptibility to breast and ovarian neoplasms and are thought t o be responsible for approximately 2.5-5% of all breast cancers. It has bee n suggested that alternative mechanisms, such as disruption of transcriptio n, may also be involved in the suppression of BRCA1 gene expression/ functi on in breast cancers. Therefore, we initiated studies on the BRCA1 transcri ptional promoter. Utilizing systematic promoter deletions and transient tra nsfection assays, a 36-base pair region was determined to be important for the positive regulation of BRCA1 transcription. Deletion of this positive r egulatory region resulted in a significant loss of promoter activity. Utili zing DNA binding assays, proteins with specific affinities for the positive regulatory region were detected. Disruption of the DNA-protein complexes c ould affect normal BRCA1 transcription and may contribute to breast cancer susceptibility.