SIRT1 in B[a]P-induced lung tumorigenesis

Abstract

Benzo[a]pyrene (B[a]P) is a carcinogen in cigarette smoke. We found that B[a]Pinduced SIRT1 in human bronchial epithelial BEAS-2B cell. SIRT1 was overexpressedin the lung of B[a]P-exposed mice and in human lung cancer biopsies. SIRT1up-regulated TNF-α and β-catenin and down-regulated the membrane fraction ofE-cadherin. In addition, SIRT1 promoted invasion, migration and tumorigenesisof BEAS-2B cells in nude mice upon B[a]P exposure. Thus, SIRT1 is involved inB[a]P-induced transformation associated with activation of the TNF-α/β-catenin axisand is as a potential therapeutic target for lung cancer.