Abstract
Expression of the breast cancer susceptibility gene, BRCA1, is induced by 17-β estradiol (E2) in estrogen receptor containing breast cancer cell lines. Our previous studies have shown that BRCA1 transcription is also regulated with the cell cycle, reaching maximal levels just before the onset of DNA synthesis. In this study, we have examined whether the estrogen induction of BRCA1 is direct or is a result of the mitogenic activity of the hormone. Four lines of evidence lead us to conclude that E2 induces BRCA1 primarily through an increase in DNA synthesis: (1) The kinetics and magnitude of induction are different from the directly E2 inducible gene, pS2; (2) Induction of BRCA1, but not pS2, is blocked by cycloheximide indicating that de novo protein synthesis is required; (3) Other hormonal and growth factor treatments that induce DNA synthesis have a similar effect, including IGF-1, EGF and DNA synthetic flares induced by tamoxifen and retinoic acid; (4) BRCA1 genomic fragments near the 5′ end of the gene containing putative estrogen response elements fail to respond to E2 when transfected into breast cancer cell lines. The most consistent explanation for these findings and other published studies is that BRCA1 transcription is induced as a result of the mitogenic activity of E2 in estrogen receptor positive cells.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Marks, J., Huper, G., Vaughn, J. et al. BRCA1 expression is not directly responsive to estrogen. Oncogene 14, 115–121 (1997). https://doi.org/10.1038/sj.onc.1200808
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1200808
Keywords
This article is cited by
-
Prognostic impact of a single-nucleotide polymorphism near the CTSO gene in hormone receptor-positive breast cancer patients
International Journal of Clinical Oncology (2016)
-
Expression profiling of estrogen responsive genes on bisphenol A, 4-nonylphenol and 17β-estradiol treatment using in house cDNA microarray
BioChip Journal (2011)
-
Transcriptional regulation of BRCA1 expression by a metabolic switch
Nature Structural & Molecular Biology (2010)
-
A role for BRCA1 in sporadic breast cancer
British Journal of Cancer (2003)
-
Regulation of BRCA1 expression and its relationship to sporadic breast cancer
Breast Cancer Research (2002)