Authors:
M Lupien, CA Meyer, ST Bailey, J Eeckhoute, J Cook, T Westerling, X Zhang, JS Carroll, DR Rhodes, XS Liu, M Brown
Journal name: 
Genes Dev
Citation info: 
24(19):2219-2227
Abstract: 
Estrogen receptor α (ERα) expression in breast cancer is predictive of response to endocrine therapy; however, resistance is common in ERα-positive tumors that overexpress the growth factor receptor ERBB2. Even in the absence of estrogen, ERα can be activated by growth factors, including the epidermal growth factor (EGF). EGF induces a transcriptional program distinct from estrogen; however, the mechanism of the stimulus-specific response is unknown. Here we show that the EGF-induced ERα genomic targets, its cistromes, are distinct from those induced by estrogen in a process dependent on the transcription factor AP-1. The EGF-induced ERα cistrome specifically regulates genes found overexpressed in ERBB2-positive human breast cancers. This provides a potential molecular explanation for the endocrine therapy resistance seen in ERα-positive breast cancers that overexpress ERBB2. These results suggest a central role for ERα in hormone-refractory breast tumors dependent on growth factor pathway activation and favors the development of therapeutic strategies completely antagonizing ERα, as opposed to blocking its estrogen responsiveness alone.
DOI: 
http://doi.org/10.1101/gad.1944810
Research group: 
Carroll Group
E-pub date: 
01 Oct 2010