| Literature DB >> 23994522 |
Chun Chen1, William T Baumann, Robert Clarke, John J Tyson.
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.Entities:
Keywords: 17β-estradiol; AKT; Breast cancer; CCS; CSC; E2; E2-bound estrogen receptor; E2:ER; EGFR; ER; ER-P; Endocrine resistance; Estrogen receptor signaling; FCS; GFR; Growth factor receptor signaling; HER2; MAPK; Mathematical modeling; NFκB; PI3K; a serine/threonine-specific protein kinase, also known as Protein Kinase B (PKB); cancer stem cell; charcoal-stripped fetal-calf serum; epidermal growth factor receptor; estrogen receptor; fetal calf serum; growth factor receptor; human epidermal growth factor receptor-2; mTOR; mammalian target of rapamycin; mitogen activated protein kinases; nuclear factor kappa-light-chain-enhancer of activated B cells; phosphatidylinositide 3-kinases; phosphorylated estrogen receptor
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Year: 2013 PMID： 23994522 PMCID： PMC3893882 DOI： 10.1016/j.febslet.2013.08.022
Source DB: PubMed Journal: FEBS Lett ISSN： 0014-5793 Impact factor: 4.124