Induction of interleukin-8 by Epstein-Barr virus latent membrane protein-1 and its correlation to angiogenesis in nasopharyngeal carcinoma
| Autor: | T, Yoshizaki, T, Horikawa, R, Qing-Chun, N, Wakisaka, H, Takeshita, T S, Sheen, S Y, Lee, H, Sato, M, Furukawa |
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| Rok vydání: | 2001 |
| Předmět: |
Transcriptional Activation
Epstein-Barr Virus Infections Herpesvirus 4 Human Binding Sites Base Sequence Neovascularization Pathologic Recombinant Fusion Proteins Interleukin-8 NF-kappa B Nasopharyngeal Neoplasms Immunohistochemistry Transcription Factor AP-1 Viral Matrix Proteins Mutation von Willebrand Factor Tumor Cells Cultured Blood Vessels Humans Angiogenesis Inducing Agents Luciferases Promoter Regions Genetic Plasmids Protein Binding |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 7(7) |
| ISSN: | 1078-0432 |
| Popis: | The EBV latent membrane protein-1 (LMP-1) is a multifunctional protein. Recently, the contribution of LMP-1 to the metastasis of nasopharyngeal carcinoma (NPC) has been suggested. Angiogenesis is a key step for metastasis. Thus, the association of LMP-1 to neovascularization of NPC was examined in this study.The association of LMP-1 to angiogenesis in 39 patients with NPC was evaluated by immunohistochemical study, and then induction of angiogenic factors by LMP-1 was examined by ELISA and luciferase reporter assay.In an immunohistochemical study, the expression of LMP-1 was significantly correlated to microvessel counts (P = 0.0003), suggesting that LMP-1 may induce some angiogenic factors. Therefore, we studied the relationship between LMP-1 expression and interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) expression by immunohistochemical analysis. IL-8, VEGF, and bFGF expression were correlated to microvessel counts, but only IL-8 expression was significantly correlated to LMP-1 expression (P0.0001). Transfection with LMP-1 expression plasmid induced IL-8 protein expression in C33A cells. The expression of LMP-1 transactivated IL-8 promoter, as demonstrated by IL-8 promoter luciferase reporter assay. Mutation of the nuclear factor kappaB responsive element in the IL-8 promoter region completely abolished transactivation by LMP-1, whereas mutation of the activator protein responsive element did not affect promoter activity.These results suggested that LMP-1 induces expression of IL-8 through the nuclear factor kappaB binding site, which may contribute in part to angiogenesis in NPC. |
| Databáze: | OpenAIRE |
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