Low Dose of Bisphenol A Modulates Ovarian Cancer Gene Expression Profile and Promotes Epithelial to Mesenchymal Transition via Canonical Wnt Pathway.
Toxicol Sci. 2018 Apr 27. Epub 2018 Apr 27. PMID: 29718440
The xenoestrogen bisphenol A (BPA) is a synthetic endocrine disrupting chemical, having the potential to increase the risk of hormone-dependent ovarian cancer. Thus, a deeper understanding of the molecular and cellular mechanisms is urgently required in the novel cell models of ovarian cancer which express estrogen receptors. To understand the possible mechanisms underlying the effects of BPA, human ovarian adenocarcinoma SKOV3 cells were exposed to BPA (10 or 100 nM) or 0.1% DMSO for 24 h, and then global gene expression profile was determined by high-throughput RNA sequencing. Also, enrichment analysis was carried out to find out relevant functions and pathways within which differentially expressed genes were significantly enriched. Transcriptomic analysis revealed 94 differential expression genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that these genes related to tumorigenesis and metastasis. Further studies were carried out to validate the results of functional annotation, which indicated that BPA (10 and 100 nM) increased migration and invasion as well as induced epithelial to mesenchymal transitions in SKOV3 and A2780 cells. Accordingly, environmentally-relevant-dose BPA activated the canonical Wnt signaling pathway. Our study first comprehensively analyzed the possible mechanisms underlying the effects of BPA on ovarian cancer. Environmentally relevant doses of BPA modulated the gene expression profile, promoted EMT progress via canonical Wnt signaling pathway of ovarian cancer.