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.
Bibliographical noteFunding 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.
- Breast cancer
- Endocrine resistance
- Estrogen receptor signaling
- Growth factor receptor signaling
- Mathematical modeling