Role of Epstein-Barr Virus Encoded Latent Membrane Protein 1 in the Carcinogenesis of Nasopharyngeal Carcinoma

查看全文 作　　者：Hui Zheng Lili Li Duosha Hu Xiyun Deng Ya [1]Cao

机构地区：[1]Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan, China;

出　　处：《Cellular & Molecular Immunology》索引2007年第4卷第3期,共12页

基　　金：grants from State Key Basic Research and Development Plan (973) of the Ministry of Science and Technology of China (2004CB518703); National High Technology Research and Development Program (863) of China (N0.2006AA02Z481); National Science Fund for Distinguished Young Scholars 0verseas (30428008); Hong Kong Cooperation Fund Project of National Natural Science Foundation of China (30418004). 摘　　要：Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) has been known to have oncogenic properties during latent infection in nasopharyngeal carcinoma (NPC). Our studies focused on the role of LMP1 in NPC, and showed that LMP1 triggers the NF-κB, AP-1 and STAT signaling pathways. Strikingly, LMP1 was found to mediate the formation of a new heterodimer between c-Jun and JunB. Also, we have identified JAK/STAT and PI-PLC-PKC activation triggered by LMP1 through upregulating the expression of JAK3 and enhancing the phosphorylation of STAT. The constitutive activation of these signaling cascades explains LMP1’s ability to induce such a diverse array of morphological and phenotypic effects in cells and provides insight into how LMP1 may induce cell transformation, in which multihit targeted genes in the downstream play an essential role. All signaling cascades triggered by LMP1 ultimately lead to the disruption of the cell cycle: the acceleration of G1/S phase and the arrest of G2/M phase. We also found that LMP1 induced the expression of hTERT and promoted cell immortalization. Importantly, by intervening physical intracellular signal transduction pathways and disturbing the progression of the cell cycle, LMP1, an important oncoprotein encoded by EBV, is thought to be a key modulator in the pathogenesis of NPC. Interfering LMP1 signaling could be a promising strategy to target the malignant phenotype of NPC. 关键词：鼻咽癌病毒感染治疗方法免疫治疗

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Role of Epstein-Barr Virus Encoded Latent Membrane Protein 1 in the Carcinogenesis of Nasopharyngeal Carcinoma

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