Chronic exposure to B[a]P induces malignant transformation of breast epithelial cells through the mechanism via TGF-β signaling pathway.

Abstract

Breast cancer has a high global incidence, and benzo[a]pyrene (B[a]P) is considered a contributing factor that increases carcinogenic risk. This study examined B[a]P's oncogenic mechanisms in mammary epithelial cells. Chronic B[a]P exposure induced morphological changes and enhanced proliferative/clonogenic capacity in MCF-10A cells. Chronic B[a]P exposure altered gene expression in MCF-10A cells, revealing differential levels of circRNAs, lncRNAs, miRNAs, and mRNAs. qRT-PCR validation demonstrated strong alignment with RNA-seq results, ensuring sequencing reliability. Additionally, chronic B[a]P exposure upregulated the protein expression of AhR and ARNT, as well as TGF-β, pSmad2/3, and KRT14, while increasing Vimentin expression and decreasing E-cadherin expression. Notably, treatment with the TGF-β inhibitor SB431542 reversed these protein expression changes in transformed cells. These results show that exposure to Chronic B[a]P induces MCF-10A cell transformation. The underlying mechanisms involve significant transcriptional alterations, AhR/ARNT expression regulation, TGF-β signaling pathway activation, KRT14 protein modulation, and EMT. Furthermore, Chronic B[a]P exposure may drive transformation through TGF-β modulation. Chronic B[a]P exposure promotes breast carcinogenesis, revealing mechanistic insights and potential preventive biomarkers.