Expression of the Epstein-Barr virus latent membrane protein 1 induces B cell lymphoma in transgenic mice
Expression of the Epstein-Barr virus latent membrane protein 1 induces B cell lymphoma in transgenic mice
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DOI：
10.1073/pnas.95.20.11963
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发表时间：
1998-09-29
影响因子：
11.1
通讯作者：
Raab-Traub, N
中科院分区：
文献类型：
--
作者：
Kulwichit, W;Edwards, RH;Raab-Traub, N
EB病毒的潜伏膜蛋白1（LMP1）在啮齿动物成纤维细胞中具有转化特性，并且在与EB病毒（EBV）感染相关的大多数癌症中表达，包括移植后淋巴瘤、霍奇金病、鼻咽癌和艾滋病相关淋巴瘤。建立了三个谱系的LMP 1转基因小鼠，其中LMP 1在IG重链启动子和增强子的控制下表达。淋巴瘤在所有三个谱系中发展，并且淋巴瘤的发病率随着年龄的增长而显著增加，在18个月以上的转基因小鼠中有42%的淋巴瘤发展。LMP1在淋巴瘤组织中呈高水平表达，而在正常淋巴组织中仅呈微量表达。IG重链的基因重排表明在所有淋巴瘤、一些淋巴样增生的脾和一些组织学正常的脾中是单克隆或寡克隆的。这些数据表明，LMP 1在没有其他EBV基因表达的情况下，在体内是致癌的，并且表明LMP 1是EBV相关淋巴瘤发展的主要促成因素。
The latent membrane protein 1 (LMP1) of the Epstein-Barr virus has transforming properties in rodent fibroblasts and is expressed in most of the cancers associated with Epstein-Barr virus (EBV) infection including posttransplant lymphomas, Hodgkin's disease, nasopharyngeal carcinoma, and AIDS-related lymphomas, In this study, three lineages of LMP1 transgenic mice were established with LMP1 expressed under the control of the Ig heavy chain promoter and enhancer. Lymphoma developed in all three lineages, and the incidence of lymphoma increased significantly with age with lymphomas developing in 42% of transgenic mice over 18 months. The expression of LMP1 was detected at high levels in the lymphoma tissues but only at trace levels in normal lymphoid tissues. Gene rearrangement of the Ig heavy chain indicated monoclonality or oligoclonality in all lymphomas, some of the lymphoid hyperplastic spleens, and some histologically normal spleens, These data reveal that LMP1, without the expression of other EBV genes, is oncogenic in vivo and indicate that LMP1 is a major contributing factor to the development of EBV-associated lymphomas.