An estrogen receptor-α/p300 complex activates the BRCA-1 promoter at an AP-1 site that binds Jun/Fos transcription factors

Repressive effects of p53 on BRCA-1 transcription

Brandon D. Jeffy, Jennifer K. Hockings, Michael Q. Kemp, Sherif S. Morgan, Jill A. Hager, Jason Beliakoff, Luke J. Whitesell, G. Timothy Bowden, Donato Romagnolo

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

One of the puzzles in cancer predisposition is that women carrying BRCA-1 mutations preferentially develop tumors in epithelial tissues of the breast and ovary. Moreover, sporadic breast tumors contain lower levels of BRCA-1 in the absence of mutations in the BRCA-1 gene. The problem of tissue specificity requires analysis of factors that are unique to tissues of the breast. For example, the expression of estrogen receptor-α (ERα) is inversely correlated with breast cancer risk, and 90% of BRCA-1 tumors are negative for ERα. Here, we show that estrogen stimulates BRCA-1 promoter activity in transfected cells and the recruitment of ERα and its cofactor p300 to an AP-1 site that binds Jun/Fos transcription factors. The recruitment of ERα/p300 coincides with accumulation in the S-phase of the cell cycle and is antagonized by the antiestrogen tamoxifen. Conversely, we document that overexpression of wild-type p53 prevents the recruitment of ERα to the AP-1 site and represses BRCA-1 promoter activity. Taken together, our findings support a model in which an ERα/AP-1 complex modulates BRCA-1 transcription under conditions of estrogen stimulation. Conversely, the formation of this transcription complex is abrogated in cells overexpressing p53.

Original languageEnglish (US)
Pages (from-to)873-882
Number of pages10
JournalNeoplasia
Volume7
Issue number9
DOIs
StatePublished - Sep 2005

Fingerprint

Transcription Factor AP-1
Estrogen Receptors
Transcription Factors
Estrogens
Breast
Breast Neoplasms
Neoplasms
Organ Specificity
Mutation
Estrogen Receptor Modulators
Estrogen Receptor alpha
Tamoxifen
S Phase
Statistical Factor Analysis
Ovary
Cell Cycle
Epithelium
Genes

Keywords

  • AP-1
  • BRCA-1
  • ERα
  • p53
  • Sporadic breast cancer

ASJC Scopus subject areas

  • Cancer Research

Cite this

An estrogen receptor-α/p300 complex activates the BRCA-1 promoter at an AP-1 site that binds Jun/Fos transcription factors : Repressive effects of p53 on BRCA-1 transcription. / Jeffy, Brandon D.; Hockings, Jennifer K.; Kemp, Michael Q.; Morgan, Sherif S.; Hager, Jill A.; Beliakoff, Jason; Whitesell, Luke J.; Bowden, G. Timothy; Romagnolo, Donato.

In: Neoplasia, Vol. 7, No. 9, 09.2005, p. 873-882.

Research output: Contribution to journalArticle

Jeffy, Brandon D. ; Hockings, Jennifer K. ; Kemp, Michael Q. ; Morgan, Sherif S. ; Hager, Jill A. ; Beliakoff, Jason ; Whitesell, Luke J. ; Bowden, G. Timothy ; Romagnolo, Donato. / An estrogen receptor-α/p300 complex activates the BRCA-1 promoter at an AP-1 site that binds Jun/Fos transcription factors : Repressive effects of p53 on BRCA-1 transcription. In: Neoplasia. 2005 ; Vol. 7, No. 9. pp. 873-882.
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