Up‐regulation of interleukin‐17 expression by human papillomavirus type 16 E6 in nonsmall cell lung cancer

• Published in: Cancer 2010-10, Vol.116 (20), p.4800-4809
• Main Authors: Chang, Yih‐Hsin, Yu, Chen‐Wei, Lai, Li‐Chuan, Tsao, Chang‐Hui, Ho, Kuo‐Ting, Yang, Shun‐Chun, Lee, Huei, Cheng, Ya‐Wen, Wu, Tzu‐Chin, Shiau, Ming‐Yuh
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Aged; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - genetics; Cell Line, Tumor; Cell Proliferation; Data processing; Female; Gene Expression Regulation, Neoplastic; Growth rate; Human papillomavirus; Human papillomavirus 16; human papillomavirus 16 E6; Humans; Immunohistochemistry; Infection; Interleukin 17; Interleukin 6; Interleukin-17 - metabolism; Interleukin-6 - metabolism; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - virology; Male; Mcl-1 protein; Mcl‐1; Medical sciences; mRNA; Myeloid Cell Leukemia Sequence 1 Protein; nonsmall cell lung cancer; Oncogene Proteins, Viral - pharmacology; Papillomaviridae - genetics; Papillomavirus Infections - genetics; Pneumology; Proto-Oncogene Proteins c-bcl-2 - metabolism; Repressor Proteins - pharmacology; Sex; Transfection; Tumor cells; Tumor Virus Infections - genetics; Tumors; Tumors of the respiratory system and mediastinum; Up-Regulation
• ISSN: 0008-543X; 1097-0142; 1097-0142
• DOI: 10.1002/cncr.25224

BACKGROUND: Human papillomavirus (HPV) 16/18 infection is associated with nonsmoking lung cancer. In this study, the authors investigated a putative correlation between interleukin (IL)‐17 expression and HPV infection in clinical nonsmall cell lung cancer (NSCLC) tissues and examined the effects of HPV infection on a human NSCLC cell line. METHODS: IL‐17 expression was investigated in 79 NSCLC tumor tissues by immunohistochemistry. Growth rate, IL‐17 mRNA, and secreting protein levels were also examined in HPV 16/18 E6‐transfected H1299 human NSCLC cells. RESULTS: Immunohistochemical data showed that 48.1% of lung tumors had IL‐17 staining, which was significantly associated with patients' sex (P = .03), HPV infection (P = .002), and tumor stage (P = .03). Significant correlations of IL‐17 with IL‐6 (P < .001) and IL‐17 with Mcl‐1 (P < .001) expression were also observed. Cell growth rate was increased, and IL‐17/Mcl‐1 expression levels were elevated in HPV 16 E6‐transfected H1299 cells. The transfected E6 oncoproteins can significantly up‐regulate expression levels of IL‐17 and antiapoptotic protein Mcl‐1. CONCLUSIONS: The study suggests that HPV infection‐induced IL‐17 levels can stimulate Mcl‐1 expression through the PI3K pathway and promote lung tumor cell progression through a p53‐ and IL‐6‐independent pathway. Cancer 2010. © 2010 American Cancer Society. Interleukin (IL)‐17 expression is significantly associated with human papillomavirus (HPV) infection in nonsmall cell lung cancer tissues. This study suggests that HPV infection‐induced IL‐17 level can stimulate Mcl‐1 expression through the PI3K pathway and promote lung tumor cell progression through a p53‐ and IL‐6–independent pathway.