An association of DNMT3b protein expression with P16INK4a promoter hypermethylation in non-smoking female lung cancer with human papillomavirus infection

• Published in: Cancer letters Vol. 226; no. 1; pp. 77 - 84
• Main Authors: Lin, Torng-Sen, Lee, Huei, Chen, Ruei-A, Ho, Ming-Lin, Lin, Chia-Yu, Chen, Ya-Hui, Tsai, Yi Yu, Chou, Ming-Chih, Cheng, Ya-Wen
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 08.08.2005; Elsevier Limited
• Subjects: Aged; Cancer therapies; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; Deoxyribonucleic acid; DNA; DNA (Cytosine-5-)-Methyltransferases - biosynthesis; DNA (Cytosine-5-)-Methyltransferases - genetics; DNA Methylation; DNA methyltransferase; DNA Methyltransferase 3B; Epigenetics; Female; Females; Gene Expression Profiling; Human papillomavirus; Humans; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - virology; Male; Medical research; Middle Aged; Papillomavirus Infections - complications; Promoter Regions, Genetic; Protein expression; Proteins; Sex Factors; Thoracic surgery; Tumorigenesis; Viral infections; DNA methyltransferase; Human papillomavirus; Lung cancer
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2004.12.031

Our recent report indicated that HPV infection may be associated with an increased frequency of p16INK4a promoter hypermethylation to cause p16 inactivation. In this study, we further speculated that the HPV infection may be linked with the expression of DNA methyltransferase (DNMT) protein in lung cancer patients and it was observed that an association of p16INK4a promoter hypermethylation with HPV infection existed, but only in female cases ( P<0.0001). Interestingly, DNMT3b protein expression was significantly correlated with p16INK4a promoter hypermethylation ( P=0.023) and HPV 16/18 infections ( P<0.001), respectively. Moreover, the correlation between p16INK4a promoter hypermethylation and DNMT3b protein expression was exclusively seen in female cases ( P=0.035). These results strongly suggested that the involvement of HPV infection in nonsmoking female lung tumorigenesis may be mediated, at least to a certain extent, through the increase of DNMT3b protein expression to cause p16INK4a promoter hypermethylation.