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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

Modeling the estrogen receptor to growth factor receptor signaling switch in human breast cancer cells

Chun Chen1, William T Baumann, Robert Clarke

  • 1Graduate Program in Genetics, Bioinformatics and Computational Biology, Virginia Polytechnic Institute & State University, Blacksburg, VA 24061, USA.

FEBS Letters
|September 3, 2013
PubMed

Insights

Breast cancer cells resist endocrine therapy by switching survival pathways. A mathematical model explains this switch, revealing how estrogen receptor (ER) and growth factor receptor (GFR) signaling interact to drive resistance.

Area of Science:

  • Oncology
  • Mathematical Biology
  • Molecular Biology

Background:

  • Breast cancer often develops resistance to endocrine therapies.
  • This resistance is linked to shifts in survival signaling pathways regulated by estrogen receptors (ER) and growth factor receptors (GFR).

Purpose of the Study:

  • To develop a mathematical model to understand the crosstalk between ER- and GFR-regulated survival signaling pathways in breast cancer.
  • To elucidate the mechanisms underlying therapy resistance in breast cancer.

Main Methods:

  • Development of a mathematical model simulating the interaction between ER and GFR signaling pathways.
  • Analysis of MCF7 cell sub-clones transfected with HER2 or EGFR.

Main Results:

  • The model accurately predicts three GFR-distribution patterns in MCF7 sub-clones.
  • It explains the reversible modulation of bimodal GFR distribution by estrogen.
  • The model demonstrates how transient ER overexpression activates GFR signaling, promoting estrogen-independent growth.

Conclusions:

  • The study provides a mechanistic understanding of the survival-signaling switch in endocrine-resistant breast cancer.
  • This knowledge can inform the development of novel therapeutic strategies to overcome treatment resistance.
Keywords:
17β-estradiolAKTBreast cancerCCSCSCE2E2-bound estrogen receptorE2:EREGFRERER-PEndocrine resistanceEstrogen receptor signalingFCSGFRGrowth factor receptor signalingHER2MAPKMathematical modelingNFκBPI3Ka serine/threonine-specific protein kinase, also known as Protein Kinase B (PKB)cancer stem cellcharcoal-stripped fetal-calf serumepidermal growth factor receptorestrogen receptorfetal calf serumgrowth factor receptorhuman epidermal growth factor receptor-2mTORmammalian target of rapamycinmitogen activated protein kinasesnuclear factor kappa-light-chain-enhancer of activated B cellsphosphatidylinositide 3-kinasesphosphorylated estrogen receptor

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