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Updated: Jun 6, 2026

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
Published on: August 12, 2015
BRCA1/BARD1 complex interacts with steroidogenic factor 1--A potential mechanism for regulation of aromatase
Yunzhe Lu1, Tao Kang, Yanfen Hu
1Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245, USA.
Abstract:
Germline mutations in BRCA1 predispose women to early onset of breast and ovarian cancers. Findings from previous studies support the notion that the tissue- and gender-specific tumor suppression function of BRCA1 is associated with its role in negative regulation of aromatase expression, the rate-limiting step in estrogen biosynthesis. The molecular mechanism of BRCA1 in regulating aromatase promoter activity remains to be elucidated. In this study, we demonstrate that, in an ovarian granulosa cell line KGN, steroidogenic factor 1 (SF-1) is required for aromatase PII promoter basal activity as well as the elevated aromatase expression mediated by BRCA1 knockdown. Furthermore, BRCA1 in KGN cells exists mainly as a heterodimer with BARD1. We provide evidence that the BRCA1/BARD1 complex interacts with SF-1 both in vivo and in vitro. However, the intrinsic ubiquitin E3 ligase activity of BRCA1/BARD1 does not appear to contribute to ubiquitynation of SF-1. We propose that the interaction between SF-1 and BRCA1/BARD1 may recruit BRCA1/BARD1 complex to the aromatase PII promoter for BRCA1/BARD1-mediate transcriptional repression.
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