SIRT1 in B[a]P-induced lung tumorigenesis

// Jianyi Lu 1, * , Min Zhang 1, * , Zhiyong Huang 2, * , Sufang Sun 1 , Yongliang Zhang 1 , Lei Zhang 1 , Lirong Peng 1 , Ailing Ma 1 , Pan Ji 1 , Jia Dai 1 , Tong Cui 1 , Heping Liu 1 , Jimin Gao 1 1 Zhejiang Provincial Key Laboratory for Technology & Application of Model Organisms, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China 2 Department of Cardiothoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China * These authors have contributed equally to this work Correspondence to: Jimin Gao, e-mail: jimingao@yahoo.com Heping Liu, e-mail: hl691296@hotmail.com Keywords: B[a]P, SIRT1, TNF-α, β-catenin, lung cancer Received: February 04, 2015      Accepted: July 16, 2015      Published: July 28, 2015 ABSTRACT Benzo[a]pyrene (B[a]P) is a carcinogen in cigarette smoke. We found that B[a]P induced SIRT1 in human bronchial epithelial BEAS-2B cell. SIRT1 was overexpressed in the lung of B[a]P-exposed mice and in human lung cancer biopsies. SIRT1 up-regulated TNF-α and β-catenin and down-regulated the membrane fraction of E-cadherin. In addition, SIRT1 promoted invasion, migration and tumorigenesis of BEAS-2B cells in nude mice upon B[a]P exposure. Thus, SIRT1 is involved in B[a]P-induced transformation associated with activation of the TNF-α/β-catenin axis and is as a potential therapeutic target for lung cancer.