Induction of epithelial-mesenchymal transition-related genes by benzo[a]pyrene in lung cancer cells

BACKGROUND. It is believed that epithelial-mesenchymal transition (EMT) occurs during the development and progression of cancer; however, the correlation between tobacco smoking and EMT remains to be elucidated. METHODS. Cells from the bronchioloalveolar carcinoma cell line A549 were exposed to benzo(a)pyrene (B[a]P) for 24 weeks, and morphology, proliferative activity, and gene expression profiles were analyzed. RESULTS. Although no apparent morphologic changes were observed, the B[a]P-exposed A549 cells exhibited enhanced proliferative activity in 1% bovine serum that contained medium, and dramatic changes in expression levels were observed in a large number of genes. Of those, the expression of EMT-related genes, such as migration-stimulating factor, plasminogen activator inhibitor-1, fibronectin, twist, transforming growth factor-β2, basic fibroblast growth factor, and electron transport system, were up-regulated; whereas gene expression of E-cadherin was decreased. Most enhanced expression levels remained 8 weeks after the retrieval of B[a]P in culture. CONCLUSIONS. The current results indicated that B[a]P seems to induce EMT in lung cancer cells, and it also may drive disease progression in patients with lung cancer.