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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

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Epigenetic and transcriptome responsiveness to ER modulation by tissue selective estrogen complexes in breast

Terri L Messier1,2, Joseph R Boyd1, Jonathan A R Gordon1,2

  • 1Department of Biochemistry, University of Vermont Larner College of Medicine, Burlington, VT, United States of America.

Plos One
|July 21, 2022
PubMed

Insights

Selective estrogen receptor modulators like bazedoxifene (BZA) can reduce breast cancer risk by altering epigenetic modifications in estrogen receptor-positive cells. BZA impacts gene expression and histone modifications, potentially restraining breast cancer development.

Area of Science:

  • Endocrinology
  • Epigenetics
  • Oncology

Background:

  • Selective estrogen receptor modulators (SERMs) are used for osteoporosis and may lower breast cancer (BCa) risk.
  • Estrogen receptor (ER) ligand administration can compromise cellular proliferation control.
  • Epigenetic mechanisms underlying hormone and SERM effects on BCa cells require elucidation.

Purpose of the Study:

  • To investigate the epigenetic impact of bazedoxifene (BZA) and estrogen compounds (E2, EC10) on gene expression and histone modifications in breast cancer cells.
  • To compare BZA's effects in ERα-positive (MCF7) and ERα-negative (MCF10A) cells.

Main Methods:

  • RNA sequencing (RNA-seq) for gene expression analysis.
  • Chromatin immunoprecipitation sequencing (ChIP-seq) to assess active (H3K4me3, H3K4ac, H3K27ac) and repressive (H3K27me3) histone modifications.
  • Treatment of MCF7 and MCF10A cells with 17β-estradiol (E2), estrogen compounds (EC10), and BZA, individually and in combination.

Main Results:

  • BZA combined with E2 or EC10 reduced estrogen-mediated histone modifications and gene expression in MCF7 ERα+ cells.
  • BZA had minimal effects on histone modifications and gene expression in MCF10A cells.
  • BZA altered H3K4ac patterns in MCF7 cells, affecting ERα target genes like GREB1 and proliferation-related genes.

Conclusions:

  • Bazedoxifene induces epigenetic changes that modulate estrogen receptor regulatory programs.
  • These BZA-induced epigenetic alterations target proliferation pathways, suggesting a mechanism for restraining breast cancer development.
  • BZA's effects are specific to ERα-positive cells, highlighting its potential in breast cancer risk reduction.

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