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Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
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Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells

Published on: February 21, 2014

ERβ1 represses FOXM1 expression through targeting ERα to control cell proliferation in breast cancer

Yoshiya Horimoto1, Johan Hartman, Julie Millour

  • 1Department of Surgery and Cancer, Imperial College, London, UK.

The American Journal of Pathology
|July 19, 2011
PubMed

Insights

Estrogen receptor beta 1 (ERβ1) suppresses breast cancer growth by inhibiting FOXM1 expression, particularly in ERα-positive cells. This research highlights ERβ1

Area of Science:

  • Oncology
  • Endocrinology
  • Molecular Biology

Background:

  • Estrogen receptor alpha (ERα) and ER beta (ERβ) play distinct roles in breast cancer.
  • The role of ERβ1 in ERα-positive breast cancer growth regulation requires further elucidation.
  • Forkhead box M1 (FOXM1) is a key oncogene implicated in breast cancer proliferation.

Purpose of the Study:

  • To investigate the functional role of ectopic estrogen receptor beta 1 (ERβ1) expression in breast cancer.
  • To determine the impact of ERβ1 on tumor growth and FOXM1 expression in vitro and in vivo.
  • To elucidate the molecular mechanisms by which ERβ1 regulates FOXM1 transcription.

Main Methods:

  • Utilized breast cancer cell lines and nude mice xenografts to study ERβ1 effects.
  • Assessed FOXM1 mRNA and protein levels via quantitative PCR and Western blotting.
  • Employed reporter gene assays and chromatin immunoprecipitation (ChIP) to analyze transcriptional regulation.
  • Investigated the interplay between ERβ1, ERα, and the FOXM1 promoter.

Main Results:

  • Ectopic ERβ1 expression suppressed tumor growth in ERα-positive breast cancer models.
  • ERβ1 repressed FOXM1 mRNA and protein expression specifically in ERα-positive cells.
  • ERβ1 directly binds to the FOXM1 promoter, repressing its transcription and displacing ERα.
  • Overexpression of FOXM1 could overcome the anti-proliferative effects of ERβ1.

Conclusions:

  • ERβ1 exerts an anti-proliferative effect in ERα-positive breast cancer by negatively regulating FOXM1.
  • FOXM1 is a critical downstream target of ERβ1 signaling in breast cancer.
  • These findings establish a novel ERβ1-FOXM1 axis with therapeutic implications for breast cancer treatment.

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