Abstract 190: Effects of bisphenol compounds on gene expression and cellular outcomes in MDA-MB-231 breast cancer cells mediated via the G protein-coupled estrogen receptor

Abstract Bisphenol A (BPA) is used in the manufacturing of various consumer products such as plastic bottles, epoxy resins in food cans, thermal printed paper, and dental sealants. BPA has been identified as an endocrine disruptor due to its ability to mimic estrogen by activating estrogen receptor signaling pathways and regulating estrogen-responsive genes through a classical estrogen receptor-mediated pathway. Concerningly, BPA is linked to health risks, such as hormone-dependent cancers, metabolic diseases, and developmental defects. What remains unclear is the effect BPA and BPA alternatives have on gene expression and cellular outcomes via interaction with a membrane-bound estrogen receptor that functions as a G protein-coupled receptor (GPER). MDA-MB-231 triple-negative breast cancer cells (TNBC) express GPER but lack the classical estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). These studies seek to determine if BPA or alternatives, functioning through GPER, differentially affect gene expression, cell proliferation, and cell migration through GPER. Preliminary studies using total RNA sequencing (RNA-Seq) identified differential gene expression patterns in cells treated with BPA or 17β -estradiol including changes in cancer-related pathways, CREB signaling, and G-protein coupled receptor-mediated pathways. Cell migration assays performed in MDA-MB-231 cells treated with BPA, BPB, BPC, or 17β -estradiol suggest that treatment with these compounds differentially affects migration, with the highest degree of migration being induced by BPC. These studies indicate that BPA and BPA alternatives differentially affect gene expression and cell migration in triple negative MDA-MB-231 breast cancer cells and exposure to these compounds may affect therapeutic outcomes in TNBC patients. Future studies will seek to clarify the role of select genes and related pathways as identified through RNA-Seq analysis in TNBC cells treated with BPA or BPA alternatives in order to clarify the role of GPER-mediated signaling in TNBC cells. Citation Format: Norman R. Estes, Cameron Sheeler, Olivia Merriam. Effects of bisphenol compounds on gene expression and cellular outcomes in MDA-MB-231 breast cancer cells mediated via the G protein-coupled estrogen receptor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 190.