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

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

doi:10.1016/j.canlet.2004.12.031

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Volume 226, Issue 1 , Pages 77-84, 8 August 2005

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

Torng-Sen Lin
- Institute of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Rd, Taichung, Taiwan, ROC
- Department of Surgery, Changhua Christian Hospital, Taichung, Taiwan, ROC
Huei Lee
- Institute of Medical and Molecular Toxicology, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Rd, Taichung, Taiwan, ROC
Ruei-A Chen
- Department of Surgery, Changhua Christian Hospital, Taichung, Taiwan, ROC
Ming-Lin Ho
- Department of Internal Medicine, Changhua Christian Hospital, Taichung, Taiwan, ROC
Chia-Yu Lin
- Department of Medicine, Zhejiang University, Zhejiang Province, People's Republic of China
Ya-Hui Chen
- Department of Surgery, Changhua Christian Hospital, Taichung, Taiwan, ROC
Yi Yu Tsai
- Institute of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Rd, Taichung, Taiwan, ROC
- Department of Ophthalmology, China Medical University Hospital, Taichung, Taiwan, ROC
Ming-Chih Chou
- Institute of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Rd, Taichung, Taiwan, ROC
- Department of Thoracic Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC
Ya-Wen Cheng
- Institute of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Rd, Taichung, Taiwan, ROC
- Corresponding author. Tel.: +886 4 24730022 11605; fax: +886 4 24723229.

Received 25 October 2004; received in revised form 8 December 2004; accepted 13 December 2004.

Abstract

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.

Keywords: DNA methyltransferase, Human papillomavirus, Lung cancer