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Updated: Oct 8, 2025

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BRCA2 represses the transcriptional activity of pS2 by E2-ERα

Mio Fukuda1, Yo Tojo2, Ami Sato2

  • 1Department of Specialized Surgeries, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.

Biochemical and Biophysical Research Communications
|December 24, 2021
PubMed

Insights

This study reveals how BRCA2 interacts with the estrogen receptor (ER) to regulate gene expression. Understanding this BRCA2-ER pathway is crucial for hereditary breast cancer research.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Germline mutations in the breast cancer 2 (BRCA2) gene are linked to hereditary breast cancer.
  • BRCA2 expression rises during the S phase of the cell cycle, aiding DNA repair.
  • The specific role of BRCA2 in estrogen-induced gene expression is not well understood.

Purpose of the Study:

  • To investigate the mechanism by which BRCA2 is activated by estrogen.
  • To identify proteins interacting with BRCA2 upon estradiol stimulation.
  • To elucidate how BRCA2 influences the transcriptional activity of estrogen-responsive genes.

Main Methods:

  • Constructed an expression plasmid to induce BRCA2 activation with estradiol.
  • Mutated transcription factor binding sites (USF1, E2F1, NF-κB) in the BRCA2 promoter.
  • Identified estrogen receptor (ER) interacting proteins using estradiol.
  • Characterized protein-BRCA2 and ER interactions.

Main Results:

  • Identified proteins that bind to BRCA2 upon estradiol addition.
  • Demonstrated that the helical domain of BRCA2 binds to activation function-2 of the ER.
  • Showed that this interaction may suppress SRC-1 coactivator binding to the pS2 gene promoter.

Conclusions:

  • BRCA2's interaction with the ER is a key regulatory mechanism in estrogen-induced gene expression.
  • This pathway involves the suppression of coactivator binding, impacting the transcription of estrogen-responsive genes like pS2.
  • Findings provide insights into BRCA2's function beyond DNA repair, particularly in the context of hormone-driven cancers.
Keywords:
Breast cancer 2EstradiolEstrogen receptorpS2

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