BRCA1 expression is not directly responsive to estrogen

Oncogene. 1997 Jan 9;14(1):115-21. doi: 10.1038/sj.onc.1200808.


Expression of the breast cancer susceptibility gene, BRCA1, is induced by 17-beta 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • BRCA1 Protein / metabolism*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Epidermal Growth Factor / pharmacology
  • Estradiol / pharmacology*
  • Estrogen Antagonists / pharmacology
  • Female
  • Genes, BRCA1 / drug effects*
  • Humans
  • Insulin-Like Growth Factor I / pharmacology
  • Molecular Sequence Data
  • Neoplasm Proteins / metabolism*
  • RNA, Messenger / metabolism
  • Receptors, Estrogen
  • Tamoxifen / pharmacology
  • Tumor Cells, Cultured / chemistry
  • Tumor Cells, Cultured / drug effects


  • BRCA1 Protein
  • Estrogen Antagonists
  • Neoplasm Proteins
  • RNA, Messenger
  • Receptors, Estrogen
  • Tamoxifen
  • Estradiol
  • Epidermal Growth Factor
  • Insulin-Like Growth Factor I

Associated data

  • GENBANK/U14680
  • GENBANK/U37574