Abstract 585: Effects of bisphenols on gene expression and cellular outcomes in MDA-MB-231 breast cancer cells mediated via G protein-coupled estrogen receptor.

Abstract Bisphenol A (BPA) is used in the manufacturing of consumer products such as plastic bottles, food-can epoxy resins, thermal printing paper, and dental sealants. BPA functions as an endocrine disruptor and can mimic estrogen through activation of estrogen receptor signaling pathways and can regulate estrogen-responsive genes through classical estrogen receptor-mediated mechanisms. BPA exposure is linked to several health risks, including hormone-dependent cancers, metabolic diseases, and developmental defects. However, the effects of BPA and its alternatives on gene expression and cellular behavior through the membrane-bound G-protein-coupled estrogen receptor (GPER) remain unclear. MDA-MB-231 triple-negative breast cancer (TNBC) cells express GPER but lack the classical estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). These studies aim to determine whether BPA and BPA alternatives, acting through GPER, differentially affect gene expression, cell proliferation, and cell migration. Preliminary RNA sequencing data show distinct gene expression changes in cells treated with BPA or 17β-estradiol, including alterations in cancer-related pathways, CREB signaling, and G-protein-coupled receptor mediated pathways. Cell migration assays performed on MDA-MB-231 cells treated with BPA, BPB, BPC, or 17β-estradiol further suggest differential effects on migration, with BPC inducing the highest degree of cell migration. These findings indicate that BPA and its alternatives influence both gene expression and cell migration in TNBC cells and may impact therapeutic outcomes in TNBC patients. Current studies focus on validating key pathways identified through RNA sequencing and clarifying the role of GPER-mediated signaling in TNBC cells exposed to BPA and BPA alternatives. Citation Format: Norman R. Estes, Cameron Sheeler. Effects of bisphenols on gene expression and cellular outcomes in MDA-MB-231 breast cancer cells mediated via G protein-coupled estrogen receptor abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 585.