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Updated: Oct 9, 2026

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
09:24

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

Role of direct interaction in BRCA1 inhibition of estrogen receptor activity

S Fan1, Y X Ma, C Wang

  • 1Department of Radiation Oncology, Long Island Jewish Medical Center, The Long Island Campus for the Albert Einstein College of Medicine, 270-05 76th Avenue, New Hyde Park, New York, NY 11040, USA.

Oncogene
|March 13, 2001
PubMed

Insights

Breast cancer-associated BRCA1 mutations impair its ability to inhibit estrogen receptor alpha (ER-alpha) activity. The BRCA1 protein interacts with ER-alpha, suggesting a role in regulating estrogen-responsive genes.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • The BRCA1 gene is known to inhibit estrogen receptor alpha (ER-alpha) transcriptional activity in cancer cell lines.
  • BRCA1 mutations are linked to breast and prostate cancer development.

Purpose of the Study:

  • To investigate how breast cancer-associated BRCA1 mutations affect its inhibitory function on ER-alpha.
  • To identify the domains of BRCA1 involved in ER-alpha inhibition and interaction.

Main Methods:

  • Overexpression of BRCA1 transgenes in various human breast and prostate cancer cell lines.
  • In vivo and in vitro binding assays to assess BRCA1-ER-alpha interaction.
  • Analysis of estrogen-regulated gene products (pS2 and cathepsin D) expression.

Main Results:

  • Breast cancer-associated BRCA1 mutations significantly reduce or abolish ER-alpha inhibition.
  • Specific domains in the amino- and carboxyl-termini of BRCA1 are crucial for ER-alpha inhibition.
  • BRCA1 directly associates with ER-alpha through an estrogen-independent interaction involving BRCA1's N-terminus and ER-alpha's AF-2 domain.
  • BRCA1 blocks the expression of endogenous estrogen-regulated genes pS2 and cathepsin D.

Conclusions:

  • The N-terminus of BRCA1 mediates interaction with ER-alpha, while the C-terminus may act as a transcriptional repression domain.
  • BRCA1's ability to inhibit ER-alpha activity is compromised by cancer-associated mutations, potentially contributing to tumorigenesis.

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