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Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
10:36

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

Published on: March 17, 2016

Estrogen-mediated down-regulation of E-cadherin in breast cancer cells

Steffi Oesterreich1, Wanleng Deng, Shiming Jiang

  • 1The Breast Center, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA. steffio@breastcancer.tmc.edu

Cancer Research
|September 23, 2003
PubMed

Insights

Estrogen down-regulates E-cadherin, a key breast tumor suppressor, by affecting its promoter activity. Antiestrogens reverse this effect, suggesting a novel mechanism in estrogen receptor-positive breast cancer.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • E-cadherin mediates cell-cell adhesion and suppresses breast tumors.
  • E-cadherin inactivation involves genetic and epigenetic mechanisms, including promoter hypermethylation and transcriptional silencing.

Purpose of the Study:

  • To investigate the effect of estrogen on E-cadherin levels in breast epithelial cells.
  • To explore the role of estrogen receptor and corepressors in regulating E-cadherin expression.

Main Methods:

  • Cell culture of normal and tumorigenic breast epithelial cells.
  • Analysis of E-cadherin promoter activity, mRNA levels, and protein expression.
  • Chromatin immunoprecipitation (ChIP) assays to assess protein binding to the E-cadherin promoter.

Main Results:

  • Estrogen significantly down-regulates E-cadherin levels in breast cells.
  • This reduction is mediated by decreased promoter activity and mRNA levels.
  • Estrogen receptor and corepressors bind to the E-cadherin promoter, with corepressor overexpression enhancing repression.

Conclusions:

  • Estrogen down-regulates E-cadherin via estrogen receptor and corepressor recruitment to its promoter.
  • This represents a novel epigenetic mechanism contributing to reduced E-cadherin in estrogen receptor-positive breast cancer.

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