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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

Genomic collaboration of estrogen receptor alpha and extracellular signal-regulated kinase 2 in regulating gene and

Zeynep Madak-Erdogan1, Mathieu Lupien, Fabio Stossi

  • 1University of Illinois, Department of Molecular and Integrative Physiology, 407 South Goodwin Ave., Urbana, IL 61801-3704, USA.

Molecular and Cellular Biology
|October 20, 2010
PubMed

Insights

Estrogen receptor alpha (ERα) and extracellular signal-regulated kinase 2 (ERK2) colocalize at gene sites in breast cancer cells. This interaction regulates gene expression and cell proliferation, revealing a novel signaling pathway.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Estrogen receptor alpha (ERα) and mitogen-activated protein kinases (MAPKs) are crucial in hormone-dependent cancers.
  • The precise interplay between ERα and MAPKs, particularly extracellular signal-regulated kinase 2 (ERK2), is not fully understood.

Purpose of the Study:

  • To investigate the interaction between estrogen-activated ERα and ERK2 in breast cancer cells.
  • To elucidate how this interaction influences gene expression and cellular processes at the genomic level.

Main Methods:

  • Chromatin immunoprecipitation sequencing (ChIP-seq) to identify genomic binding sites.
  • Western blotting and immunofluorescence to assess protein activation and localization.
  • Analysis of gene expression and cell cycle progression.

Main Results:

  • Estrogen-occupied ERα activates and interacts with ERK2, leading to their colocalization at chromatin binding sites in breast cancer cells.
  • This colocalization predominantly occurs at distal enhancer sites and is essential for ERK2's modulation of estrogen-dependent gene expression and proliferation.
  • The ERK2 substrate CREB1 is activated and recruited to chromatin, cooperating with ERα/ERK2 to regulate transcription and cell cycle.

Conclusions:

  • A novel mechanism of convergence between ERK2 and ERα at the chromatin level has been identified.
  • ERK2 directly supports nuclear receptor activities, suggesting a broader role for MAPKs in regulating gene expression via other nuclear receptors.

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