This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Cheng, Y.-W. Articles by Chang, Y.-H. PubMed PubMed Citation Articles by Cheng, Y.-W. Articles by Chang, Y.-H.

Human Papillomavirus Type 16/18 Up-Regulates the Expression of Interleukin-6 and Antiapoptotic Mcl-1 in Non–Small Cell Lung Cancer

Authors' Affiliations: Institutes of ¹ Medicine; ² Medical and Molecular Toxicology, Chung Shan Medical University; ³ Hung Kuang University; ⁴ Department of Internal Medicine, Chung Shan Medical University Hospital; and ⁵ School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan, Republic of China

Requests for reprints: Yih-Hsin Chang, School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan, Republic of China. Phone: 886-4-24730022, ext. 11718; Fax: 886-4-23248171; E-mail: cyh{at}csmu.edu.tw.

Purpose: Human papillomavirus (HPV) 16/18 infection is reported to be associated with nonsmoking Taiwanese female lung cancer. In this study, we attempted to further reveal the association between HPV infection with Mcl-1 and interleukin (IL)-6 expressions and to elucidate the roles of HPV infection in lung tumorigenesis.

Experimental Design: IL-6 and Mcl-1 expressions were investigated in 79 tumor tissues from lung cancer patients by immunohitochemistry. Secreting IL-6 levels and Mcl-1 expressions were examined by ELISA and Western blot, respectively, in HPV 16/18 E6- and E7-transfected A549 human lung cancer cells, as well as in the HPV16-infected TL-1 lung cancer cells established from lung cancer patients.

Results: Lung tumors (70.9% and 57.0%) had positive IL-6 and Mcl-1 immunostainings, respectively. Significant correlation between IL-6 and Mcl-1 expression were observed (P < 0.0001). Both IL-6 and Mcl-1 expression were significantly associated with HPV 16/18 infection (P = 0.014 and P = 0.004, respectively). IL-6 and Mcl-1 protein levels were not only elevated in HPV 16/18 E6- and E7-transfected A549 cells but also in TL-1 cells. Phosphatidylinositol-3-OH kinase pathway was the major pathway contributing to the up-regulation of Mcl-1 by IL-6 in HPV-infected lung cancer cells.

Conclusions: The up-regulating effects of HPV 16/18 E6 and E7 to IL-6 and Mcl-1 expressions were observed in E6- and E7-transfected A549 cells and in HPV16-infected TL-1 cells, mainly through the phosphatidylinositol-3-OH kinase pathway. The involvement of HPV infection in lung tumorigenesis may be partly through a concomitant increased expression of autocrine and/or paracrine IL-6 and the downstream Mcl-1.