Epstein-Barr virus (EBV) latent membrane protein 1 induces interleukin-8 through the nuclear factor-kappa B signaling pathway in EBV-infected nasopharyngeal carcinoma cell line.
OBJECTIVE
Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic malignant tumor and is associated with Epstein-Barr virus (EBV) infection that exhibits type II latency. Angiogenesis is essential for tumor growth, invasion, and metastasis. Our previous studies have indicated that interleukin (IL)-8 was over-expressed in many NPC tissues and was found to be significantly correlated with angiogenesis by immunohistochemistry.


METHODS
In vitro design.


METHODS
The influence of the EBV genome for IL-8 gene expression was studied using the EBV-genome-positive and -negative epithelial/NPC hybrid cell line NPC-KT. The EBV-positive and -negative clones were selected by polymerase chain reaction and in situ hybridization.


RESULTS
EBV-positive clones expressed abundant IL-8 mRNA compared with EBV-negative clones. This result indicated that over-expression of IL-8 depended on the presence of EBV genomes in NPC-KT cells. Two encoded genes, latent membrane protein (LMP)1 and EBV-encoded small RNAs (EBERs), expressed in NPC were transfected in EBV-negative NPC-KT cells. LMP1 transactivated the IL-8 promoter, whereas EBERs did not. Moreover, the nuclear factor (NF)-kappa B binding site in the IL-8 promoter was essential for the response to LMP1, and the activator protein (AP)-1 binding site played only a partial role.


CONCLUSIONS
LMP1 induces IL-8 mainly through the activation of NF-kappa B and partly through AP-1 in NPC model cell lines, NPC-KT, and this suggests that LMP1 plays an important role in the angiogenesis of NPC.
Ren
Qingchun
Q
Division of Otolaryngology, Graduate School of Medicine, and Department of Molecular Oncology and Virology, Cancer Research Institute, Kanazawa University, Takaramachi, Kanazawa, Japan.
Sato
Hiroshi
H
Murono
Shigeyuki
S
Furukawa
Mitsuru
M
Yoshizaki
Tomokazu
T
D015152:Blotting, Northern; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D045744:Cell Line, Tumor; D019976:Cloning, Organism; D020031:Epstein-Barr Virus Infections / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D010957:Plasmids / Q000235:genetics; D017354:Point Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D014162:Transfection / Q000379:methods; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000378:metabolism
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D014763:Viral Matrix Proteins