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

Chun Chen, William T. Baumann, Robert Clarke, John J. Tyson

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Breast cancer cells develop resistance to endocrine therapies by shifting between estrogen receptor (ER)-regulated and growth factor receptor (GFR)-regulated survival signaling pathways. To study this switch, we propose a mathematical model of crosstalk between these pathways. The model explains why MCF7 sub-clones transfected with HER2 or EGFR show three GFR-distribution patterns, and why the bimodal distribution pattern can be reversibly modulated by estrogen. The model illustrates how transient overexpression of ER activates GFR signaling and promotes estrogen-independent growth. Understanding this survival-signaling switch can help in the design of future therapies to overcome resistance in breast cancer.

Original languageEnglish (US)
Pages (from-to)3327-3334
Number of pages8
JournalFEBS Letters
Volume587
Issue number20
DOIs
StatePublished - Oct 11 2013
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported in part by the US National Institutes of Health Grant U54-CA149147 (to R.C., J.J.T. and W.T.B.), and by fellowships to C.C. provided by the Virginia Polytechnic Institute and State University graduate program in Genetics, Bioinformatics and Computational Biology.

Keywords

  • Breast cancer
  • Endocrine resistance
  • Estrogen receptor signaling
  • Growth factor receptor signaling
  • Mathematical modeling

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