Record Details

Growth Factor Stimulation Induces a Distinct ERalpha Cistrome Underlying Breast Cancer Endocrine Resistance

Harvard Dataverse (Africa Rice Center, Bioversity International, CCAFS, CIAT, IFPRI, IRRI and WorldFish)

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Title Growth Factor Stimulation Induces a Distinct ERalpha Cistrome Underlying Breast Cancer Endocrine Resistance
 
Identifier https://doi.org/10.7910/DVN/DHHH0Y
 
Creator Mathieu Lupien
Clifford Meyer
et al.
 
Publisher Harvard Dataverse
 
Description INSTRUCTIONS: Please enter one of the following Topic Classifications in the section below: Bioinformatics
& Computational Biology Genes & Environment Genetic & Molecular Epidemiology Medical Genomics Molecular Genetics Proteomics Statistical Genetics, Genomics, and Omics
Estrogen receptor a (ERa) expression in breast cancer is predictive of response to endocrine therapy; however,resistance is common in ERa-positive tumors that overexpress the growth factor receptor ERBB2. Even in the absence of estrogen, ERa 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 ERa genomic targets, its cistromes, are distinct from those induced by estrogen in a process dependent on the transcription factor AP-1. The EGF-induced ERa cistrome specifically regulates genes found overexpressed in ERBB2-positive human breast cancers. This providesa potential molecular explanation for the endocrine therapy resistance seen in ERa-positive breast cancers that overexpress ERBB2. These results suggest a central role for ERa in hormone-refractory breast tumors dependent on growth factor pathway activation and favors the development of therapeutic strategies completely antagonizing ERa, as opposed to blocking its estrogen responsiveness alone. [Keywords: ERBB2; breast cancer; cistrome; estrogen receptor; growth factors; transcription]