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Discover Oncology
Published in: Discover Oncology 2/2017

01-04-2017 | Original Paper

Bisphenol A Induces Sox2 in ER+ Breast Cancer Stem-Like Cells

Authors: M. Angeles Lillo, Cydney Nichols, Tiffany N. Seagroves, Gustavo A. Miranda-Carboni, Susan A. Krum

Published in: Discover Oncology | Issue 2/2017

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Abstract

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.
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Metadata
Title
Bisphenol A Induces Sox2 in ER+ Breast Cancer Stem-Like Cells
Authors
M. Angeles Lillo
Cydney Nichols
Tiffany N. Seagroves
Gustavo A. Miranda-Carboni
Susan A. Krum
Publication date
01-04-2017
Publisher
Springer US
Published in
Discover Oncology / Issue 2/2017
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI
https://doi.org/10.1007/s12672-017-0286-5

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