Kulwichit W, Edwards R H, Davenport E M, Baskar J F, Godfrey V, Raab-Traub N
Lineberger Comprehensive Cancer Center, Microbiology and Immunology, and Pathology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.
Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11963-8. doi: 10.1073/pnas.95.20.11963.
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.
爱泼斯坦-巴尔病毒的潜伏膜蛋白1（LMP1）在啮齿动物成纤维细胞中具有转化特性，并且在大多数与爱泼斯坦-巴尔病毒（EBV）感染相关的癌症中表达，包括移植后淋巴瘤、霍奇金病、鼻咽癌和艾滋病相关淋巴瘤。在本研究中，利用在Ig重链启动子和增强子控制下表达LMP1的方法，建立了三个LMP1转基因小鼠品系。所有三个品系均发生了淋巴瘤，淋巴瘤的发病率随年龄显著增加，18个月以上的转基因小鼠中有42%发生了淋巴瘤。在淋巴瘤组织中检测到LMP1的高表达，但在正常淋巴组织中仅检测到微量表达。Ig重链的基因重排表明，所有淋巴瘤、一些淋巴样增生性脾脏和一些组织学正常的脾脏均为单克隆性或寡克隆性。这些数据表明，在没有其他EBV基因表达的情况下，LMP1在体内具有致癌性，并表明LMP1是EBV相关淋巴瘤发生的主要促成因素。
