1. Transcriptome analysis of human mammary epithelial cells treated with bisphenol A and bisphenol A analogue mixtures reveals major alterations in multiple cellular pathways
- Author
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Robin Mesnage, Helin Omriouate, and Michael Antoniou
- Subjects
breast cancer ,transcriptome ,bisphenol ,Toxicology. Poisons ,RA1190-1270 - Abstract
Introduction Bisphenol A (BPA) is used in the manufacture of polycarbonate plastics and resins employed in the packaging of food, drink and other products. BPA is a proven endocrine disruptive chemical and due to increasing public concern and regulatory restrictions, is frequently replaced by structurally similar bisphenols. In this study, the action of BPA and a mixture of BPA-analogues on cell proliferation and the transcriptome were compared in three human mammary epithelial cell lines, estrogen receptor positive MCF-7 and MCF-12A, and estrogen receptor negative MCF-10A. Methods Cells were exposed to varying concentrations of BPA and BPA-analogue mixtures (BPAF, BPAP, BPB, BPF, BPS and BPZ with and without BPA). Estrogenic potential was assessed by a cell proliferation assay. Transcriptome profiling was realized by sequencing cDNA prepared from total mRNA. Results BPA and BPA-analogue mixtures caused limited change in cell proliferation. In contrast, many genes were differentially expressed in MCF-10A compared to MCF-7 and MCF-12A cells. KEGG pathway enrichment analysis identified several pathways in MCF-10A cells dysregulated by BPA and bisphenol mixtures with the most overrepresented being protein processing in the endoplasmic reticulum, spliceosome function and ubiquitin-mediate proteolysis. Conclusions Gene expression profiles in MCF-10A cells revealed potential new mechanisms of toxicity from BPA and its analogues. Overall, results obtained suggest that investigation into mechanisms of toxicity and biochemical pathways affected by BPA and its analogues needs to be undertaken with different types of human mammary epithelial cells and omics analytical methods to highlight any role in breast cancer initiation and progression.
- Published
- 2022
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