Abstract 3192: The environmental estrogen bisphenol A (BPA) regulates mammary gland stem cells

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA A study by the Centers for Disease Control revealed detectable levels of the environmental toxin Bisphenol A (BPA) in urine samples from over 92% of people in the NHANES (National Health and Nutrition Examination Survey) study. BPA is a small molecule used in the polymerization of polycarbonate plastics. These plastics are widely used in food containers, water bottles, dental fillings and toys, among many other products. BPA is similar to the synthetic estrogen diethylstilbesterol (DES) and can bind to estrogen receptor alpha (ERα) or estrogen receptor beta (ERβ). Because BPA is lipophilic and has been detected in mammary gland fat in humans, we hypothesize that BPA is an estrogen mimic in the stromal adipocytes in the breast and can induce stem cell proliferation and survival, leading to breast tumor formation. Indeed, BPA increases the size and number of mammospheres from normal mouse mammary gland and from human MCF7 breast cancer cells. Adipocytes co-cultured with mammospheres increased the size of the spheres, and BPA further increased the size of adipocyte co-cultured mammospheres. BPA upregulates the stem cell markers Nanog, OCT4 and SOX2 in mammospheres. ERα and pCREB were shown to bind to an enhancer downstream of the SOX2 gene after BPA treatment. Finally, BPA increased the size of tumor xenografts in NUDE mice. Together these experiments demonstrate that BPA may induce breast cancer via ERα and pCREB regulation of breast cancer stem cells. Citation Format: Cydney Nichols, Xiangming Ding, Gustavo Miranda-Carboni, Susan Amy Krum. The environmental estrogen bisphenol A (BPA) regulates mammary gland stem cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3192. doi:10.1158/1538-7445.AM2014-3192