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Modeling the estrogen receptor to growth factor receptor signaling switch in human breast cancer cells
Author(s) -
Chen Chun,
Baumann William T.,
Clarke Robert,
Tyson John J.
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.08.022
Subject(s) - estrogen receptor , crosstalk , breast cancer , signal transduction , cancer research , estrogen , receptor , estrogen receptor alpha , transfection , estrogen receptor beta , biology , microbiology and biotechnology , endocrinology , medicine , cancer , cell culture , genetics , physics , optics
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.