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

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.