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Epstein-Barr virus encoded latent membrane protein 1 induces TRAF1 expression to promote anti-apoptosis activity via NF-κB signaling pathway in nasopharyngeal carcinoma
作者姓名:Wang C  Ai M  Ren W  Xiao H  Li X  Tang F  Gu H  Yi W  Weng X  Deng X  Cao Y
作者单位:[1]DepartmentofOralandMaxillofacialSurgery,XiangYaHospital,CentralSouthernUniversity,Changsha410078,China [2]CancerResearchInstitute,CentralSouthernUniversity,Changsha410078,China
基金项目:StateKeyBasicResearchProgram,FundamentalInvestigationonHumanCarcinogenesis (No .G19980 5 12 0 1),NationalScienceFundforDistinguishedYoungScholars (No .3 95 2 5 0 2 2 ),theNationalNaturalScienceFoundationofChina (No 3 0 10 0 0 0 5 )
摘    要:Objectives To identify whether Epstein-Barr virus (EBV) encoded latent membrane protein 1(LMP1) can induce tumor necrosis factor receptor-associated factor 1 (TRAF1) expression and promote its anti-apoptosis activity via the NF-KB signaling pathway, and assess that LMP1 suppresses apoptosis in nasopharyngeal carcinoma (NPC).Methods A stable transfected cell line HNE2-LMP1 was established by introducing LMP1 cDNA into HNE2 cells. Transactivation of TRAF1 was determined by luciferase reporter assay, while expression of TRAF1 mRNA was detected by RT-PCR and expression of TRAF1 protein and caspase 3 by Western blot analysis. Apoptosis activity was observed through fluorescence staining.Results LMP1 induced TRAF1 expression in NPC cells and caused a decrease in apoptosis. This induction could be blocked by antisense LMPI. Moreover, LMPl-mediated induction of a TRAF1 promoter-driven reporter gene was significantly impaired when the KB site KB1 or KB5 was disrupted,whereas mutation of κB3 had only a minor effect on LMP1 dependent up-regulation of the reporter gene.Conclusion LMP1 induces TRAF1 expression and promotes its anti-apoptosis activity via the NF-κB signaling pathway, which may be one of the mechanisms that LMP1 uses to suppress apoptosis in NPC cells.

关 键 词:鼻咽癌  抗细胞凋亡  EB病毒  潜伏膜蛋白-1  肿瘤坏死因子受体相关因子-1  NF-κB  信号转导

Epstein-Barr virus encoded latent membrane protein 1 induces TRAF1 expression to promote anti-apoptosis activity via NF-kappaB signaling pathway in nasopharyngeal carcinoma
Wang C,Ai M,Ren W,Xiao H,Li X,Tang F,Gu H,Yi W,Weng X,Deng X,Cao Y.Epstein-Barr virus encoded latent membrane protein 1 induces TRAF1 expression to promote anti-apoptosis activity via NF-kappaB signaling pathway in nasopharyngeal carcinoma[J].Chinese Medical Journal,2003,116(7):1022-1028.
Authors:Wang Chengxing  Ai Midan  Ren Wei  Xiao Hui  Li Xiaoyan  Tang Faqing  Gu Huanhua  Yi Wei  Weng Xinxian  Deng Xiyun  Cao Ya
Institution:1. Department of Oral and Maxillofacial Surgery, Xiang Ya Hospital, Central Southern University, Changsha 410078, China
2. Cancer Research Institute, Central Southern University, Changsha 410078, China
Abstract:OBJECTIVES: To identify whether Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) can induce tumor necrosis factor receptor-associated factor 1 (TRAF1) expression and promote its anti-apoptosis activity via the NF-kappaB signaling pathway, and assess that LMP1 suppresses apoptosis in nasopharyngeal carcinoma (NPC). METHODS: A stable transfected cell line HNE2-LMP1 was established by introducing LMP1 cDNA into HNE2 cells. Transactivation of TRAF1 was determined by luciferase reporter assay, while expression of TRAF1 mRNA was detected by RT-PCR and expression of TRAF1 protein and caspase 3 by Western blot analysis. Apoptosis activity was observed through fluorescence staining. RESULTS: LMP1 induced TRAF1 expression in NPC cells and caused a decrease in apoptosis. This induction could be blocked by antisense LMP1. Moreover, LMP1-mediated induction of a TRAF1 promoter-driven reporter gene was significantly impaired when the kappaB site kappaB1 or kappaB5 was disrupted, whereas mutation of kappaB3 had only a minor effect on LMP1 dependent up-regulation of the reporter gene. CONCLUSION: LMP1 induces TRAF1 expression and promotes its anti-apoptosis activity via the NF-kappaB signaling pathway, which may be one of the mechanisms that LMP1 uses to suppress apoptosis in NPC cells.
Keywords:nasopharyngeal carcinoma * Epstein-Barr virus * TRAF1 * NF-κB * caspase 3
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