Bisphenol A Induces Sox2 in ER+ Breast Cancer Stem-Like Cells
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Bisphenol A (BPA) is an endocrine disrupting compound used in food and beverage plastic containers and has been shown to increase breast cancer cellular proliferation. However, the concentrations of BPA used in these experiments are far higher than the physiological levels of BPA detected in the human body. We observed in vitro that exposure of MCF-7 cells to physiological concentrations of BPA failed to increase cell proliferation or to induce canonical estrogen-responsive genes (pS2 and progesterone receptor (PR)), in contrast to 17β-estradiol (E2) treatment. However, MCF-7 cells treated with 10 nM BPA induced ALDH1 expression, a marker of human mammary stem cells. When treated with 10 nM BPA, mammospheres derived either from MCF-7 cells, a patient-derived xenograft, or the normal mouse mammary gland exhibited increased size; however, these effects were not observed in MDA-MB-231 mammospheres. Mechanistically, BPA induced SOX2 mRNA and protein in MCF-7 mammospheres, resulting from enhanced CREB phosphorylation, and subsequent binding of pCREB to a SOX2 downstream enhancer. These findings suggest that physiological levels of BPA increase estrogen receptor-positive breast cancer tumor maintenance through enhanced cancer stem-like cell activity via direct regulation of SOX2 transcription.
KeywordsCancer Stem Cell SOX2 Expression Breast Cancer Stem Cell Mammary Stem Cell Breast Stem Cell
This work was supported by a grant from Susan G. Komen for the Cure to SAK (KG110317); the National Cancer Institute (CA138488 to T.N.S.); and intramural support from the West Cancer Center in Memphis, TN (to T.N.S.).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
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