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BRCA1 expression is not directly responsive to estrogen.

Publication ,  Journal Article
Marks, JR; Huper, G; Vaughn, JP; Davis, PL; Norris, J; McDonnell, DP; Wiseman, RW; Futreal, PA; Iglehart, JD
Published in: Oncogene
January 9, 1997

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.

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Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

January 9, 1997

Volume

14

Issue

1

Start / End Page

115 / 121

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Tamoxifen
  • Receptors, Estrogen
  • RNA, Messenger
  • Oncology & Carcinogenesis
  • Neoplasm Proteins
  • Molecular Sequence Data
  • Insulin-Like Growth Factor I
  • Humans
  • Genes, BRCA1
 

Citation

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Marks, J. R., Huper, G., Vaughn, J. P., Davis, P. L., Norris, J., McDonnell, D. P., … Iglehart, J. D. (1997). BRCA1 expression is not directly responsive to estrogen. Oncogene, 14(1), 115–121. https://doi.org/10.1038/sj.onc.1200808
Marks, J. R., G. Huper, J. P. Vaughn, P. L. Davis, J. Norris, D. P. McDonnell, R. W. Wiseman, P. A. Futreal, and J. D. Iglehart. “BRCA1 expression is not directly responsive to estrogen.Oncogene 14, no. 1 (January 9, 1997): 115–21. https://doi.org/10.1038/sj.onc.1200808.
Marks JR, Huper G, Vaughn JP, Davis PL, Norris J, McDonnell DP, et al. BRCA1 expression is not directly responsive to estrogen. Oncogene. 1997 Jan 9;14(1):115–21.
Marks, J. R., et al. “BRCA1 expression is not directly responsive to estrogen.Oncogene, vol. 14, no. 1, Jan. 1997, pp. 115–21. Pubmed, doi:10.1038/sj.onc.1200808.
Marks JR, Huper G, Vaughn JP, Davis PL, Norris J, McDonnell DP, Wiseman RW, Futreal PA, Iglehart JD. BRCA1 expression is not directly responsive to estrogen. Oncogene. 1997 Jan 9;14(1):115–121.

Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

January 9, 1997

Volume

14

Issue

1

Start / End Page

115 / 121

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Tamoxifen
  • Receptors, Estrogen
  • RNA, Messenger
  • Oncology & Carcinogenesis
  • Neoplasm Proteins
  • Molecular Sequence Data
  • Insulin-Like Growth Factor I
  • Humans
  • Genes, BRCA1