Human papillomavirus type 16/18 up-regulates the expression of interleukin-6 and antiapoptotic Mcl-1 in non-small cell lung cancer.

Abstract

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 immunohistochemistry. 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.

• Authors: Ya-Wen Cheng, Huei Lee, Ming-Yuh Shiau, Tzu-Chin Wu, Tsung-Teng Huang, Yih-Hsin Chang
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 14 Issue 15 Pg. 4705-12 (Aug 01 2008) ISSN: 1078-0432 [Print] United States
• PMID: 18676738 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-6
• Myeloid Cell Leukemia Sequence 1 Protein
• Proto-Oncogene Proteins c-bcl-2

Topics

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Non-Small-Cell Lung (metabolism)
• Cell Line, Tumor
• Female
• Gene Expression Regulation, Neoplastic
• Gene Expression Regulation, Viral
• Human papillomavirus 16 (metabolism)
• Human papillomavirus 18 (metabolism)
• Humans
• Interleukin-6 (biosynthesis)
• Lung Neoplasms (metabolism)
• Male
• Middle Aged
• Myeloid Cell Leukemia Sequence 1 Protein
• Proto-Oncogene Proteins c-bcl-2 (biosynthesis)