Abstract:

Abstract:Objective
To study the role of p16 in cigarette smoking-induced lung carcinogenesis by detecting the expression of p16 in human normal bronchial epithelial cells（HBE） after exposure to cigarette smoke extracts (CSE) and analyze the underlying mechanism.Methods HBE were treated with various doses of CSE or control DMSO and the protein and mRNA levels of p16 were determined by Western blotting and Realtime RT-PCR respectively.The genomic promoter of p16 was cloned and its transcriptional activity after exposure to CSE was determined by luciferase assay.Results  After the treatment of different doses (0,10,25,50,100 mg•L^-1) of CSE,the mRNA and protein levels in HBE were significantly inhibited in a dose-dependent manner.More than 25 mg•L^-1 of CSE conld significantly inhibit the  p16 mRNA and protein levels,there was significant difference compared with control group(P<0.05).100 mg•L^-1 of CSE showed the greatest inhibiory effect. Moreover,the transcriptional activity of the promoter of p16 was significantly suppressed by more than 25 mg•L^-1 CSE,there was significant difference compared with control group(P<0.05).Conclusion Cigarette smoke extracts can inhibit the expression of p16 by suppressing its transcriptional activity,indicating that p16 might play a key role in cigarette smoking-induced lung carcinogenesis.

Key words: cigarette smoke extracts；lung neoplasms；p16 gene