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Epstein‐Barr Virus (EBV) Latent Membrane Protein 1 Induces Interleukin‐8 through the Nuclear Factor‐κB Signaling Pathway in EBV‐Infected Nasopharyngeal Carcinoma Cell Line
Author(s) -
Ren Qingchun,
Sato Hiroshi,
Murono Shigeyuki,
Furukawa Mitsuru,
Yoshizaki Tomokazu
Publication year - 2004
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1097/00005537-200405000-00012
Subject(s) - nasopharyngeal carcinoma , epstein–barr virus , biology , angiogenesis , microbiology and biotechnology , cell culture , virus , bzlf1 , cancer research , transfection , virology , herpesviridae , medicine , genetics , viral disease , radiation therapy
Background/Objectives: 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. Study Design: 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)‐ κB 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‐κB 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.