AJBM Volume 2, Issue 2, pages 224–237, February 2014 Full Text-PDF
Keith Jeng, Marisa Chang, Steve Pili, Christian Ellis, Kebba Dhanda, Xing Lee, and Per Fielding
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