Up-regulation of interleukin-17 expression by human papillomavirus type 16 E6 in nonsmall cell lung cancer.
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.
Chang
Yih-Hsin
YH
School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taiwan, Republic of China.
Yu
Chen-Wei
CW
Lai
Li-Chuan
LC
Tsao
Chang-Hui
CH
Ho
Kuo-Ting
KT
Yang
Shun-Chun
SC
Lee
Huei
H
Cheng
Ya-Wen
YW
Wu
Tzu-Chin
TC
Shiau
Ming-Yuh
MY
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000821:virology*; D008297:Male; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009856:Oncogene Proteins, Viral / Q000494:pharmacology*; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012097:Repressor Proteins / Q000494:pharmacology*; D014162:Transfection; D014412:Tumor Virus Infections / Q000235:genetics*; D015854:Up-Regulation
C068651:E6 protein, Human papillomavirus type 16; D020381:Interleukin-17; D015850:Interleukin-6; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009856:Oncogene Proteins, Viral; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins