Mechanistic links between HPV16/18 E6 and lung cancer


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Keith Jeng 1, Marisa Chang 1, Steve Pili 1, Christian Ellis 2, Kebba Dhanda 2, Xing Lee 3,  Per Fielding 1*
Author Affiliations
∗Correspondence author e-mail: behnamzamanzad5@gmail.com: 1Division of Thoracic Surgery, Columbia University. 2Biochemistry Department, Institute for Molecular Virology, University of Minnesota, 3Department of Pathology, China Medical University Hospital, Taiwan

 

Abstract

Lung cancer has emerged as a global public health issue. Recent studies have consistently linked the presence of HPV16/18 E6 to the development of lung cancer as oncoproteins. HPV16/18 E6 and E7 have been shown to regulate the expression of various target genes and proteins including p53/pRb, VEGF, HIF-1α, cIAP-2, and hTERT, and contribute to cell proliferation, angiogenesis, and cell immortalization. We hypothesized that HPV16/18 E6 links to development of lung cancer through activation of HIF-1α/ VEGF signaling. Lung cancer patients eligible for surgical treatment were tested for the presence of HPV16/18 E6 in excised tumor tissue. HPV16/18 E6 detection and genotyping was performed using facility of a polymerase chain reaction and immunohistochemistry. Of the 292 tumor samples tested, 98 samples showed presence of HPV16/18 E6, and significantly, high in nonsmoker patients. Furthermore, overexpression of HPV16/18 E6 associated with increased level of HIF-1α and VEGF, that demonstrated by using reporter gene assays. We conclude that HPV16/18 E6 is strongly associated with lung cancer and might represent novel therapeutic targets to manage lung cancer.

Key words: Lung cancer; HPV16/18 E6; HIF-1α; VEGF; Immunohistochemistry

Copyright © 2014 by The American Society for BioMedicine and BM-Publisher, Inc.

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Review Article
DOI: http://dx.doi.org/10.18081/2333-5106/014-08/199-212
American Journal of BioMedicine 2014, Volume 2, Issue 3, pages 199-212
Received 11 April 2014; accepted July 20, 2014, Published August 27, 2014

How to cite this article
Jeng k, Chang M, Pili S, Ellis C, Dhanda K, Lee X, Fielding P. Mechanistic links between HPV16/18 E6 and lung cancer. American Journal of BioMedicine 2014;2(3):199-212.

Case report outline
1. Abstract
2. Keywords
3. Introduction
4. Methods
5. Results
6. Discussion
7. References

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