Related Experiment Video

Updated: Oct 5, 2026

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
09:07

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay

Published on: December 19, 2018

BRCA1 mediates ligand-independent transcriptional repression of the estrogen receptor

L Zheng1, L A Annab, C A Afshari

  • 1Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center, San Antonio 78245, USA. leew@uthscsa.edu

Proceedings of the National Academy of Sciences of the United States of America
|August 9, 2001
PubMed

Insights

Mutational inactivation of BRCA1 increases cancer risk. BRCA1 normally represses estrogen receptor alpha (ERalpha) activity, preventing inappropriate cell growth in breast and ovarian tissues.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Mutational inactivation of BRCA1 is linked to increased breast and ovarian cancer risk.
  • The tissue-specific tumor-suppressive functions of BRCA1 are not fully understood.
  • Estrogen receptor alpha (ERalpha) plays a key role in the normal function and proliferation of breast and ovarian tissues.

Purpose of the Study:

  • To investigate the mechanism by which BRCA1 exerts its tissue-restricted tumor-suppressive effects.
  • To determine the relationship between BRCA1 and estrogen receptor alpha (ERalpha) in the context of cancer development.

Main Methods:

  • Utilized Brca1-null mouse embryo fibroblasts and BRCA1-deficient human ovarian cancer cells.
  • Performed ectopic expression of wild-type and mutant BRCA1.
  • Conducted chromatin immunoprecipitation assays in human breast cancer cells.

Main Results:

  • BRCA1 mediates ligand-independent transcriptional repression of ERalpha.
  • BRCA1 deficiency leads to ligand-independent ERalpha activity in specific cell types.
  • Wild-type BRCA1, but not mutants, restored ERalpha repression, dependent on histone deacetylase activity.
  • BRCA1 associates with ERalpha at estrogen-response elements prior to estrogen stimulation.

Conclusions:

  • BRCA1 acts as a barrier to ERalpha transcriptional activation by unliganded ERalpha.
  • BRCA1 inactivation may promote tumorigenesis via dysregulated hormonal control of epithelial cell proliferation.

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