多瘤病毒T抗原致癌基因制备转基因动物模型的研究进展  

Transgenic animal models induced by polyomavirus

作　　者：王建平[1] 聂小毳[1] 郑华川[1] 

机构地区：[1]中国医科大学基础医学院生物化学与分子生物学研究室,病理与病理生理学研究所,辽宁沈阳110001

出　　处：《中华肿瘤防治杂志》2012年第19期1516-1520,共5页Chinese Journal of Cancer Prevention and Treatment

基　　金：人事部留学人员科技活动择优资助项目(2008-01);教育部留学归国人员启动项目(2009-03);辽宁省百千万人才计划资助项目(2008921066);沈阳市科技攻关项目(1091175-1-00)

摘　　要：目的:总结多瘤病毒基因结构与功能,深入分析多瘤病毒T抗原在转基因动物模型中的研究进展。方法:应用PubMed数据库检索系统,以"SV40virus、simian virus40、JC virus、John Cunningham virus和BK virus"为关键词,检索1990-2011的相关文献,共检索到英文文献23 254条。纳入标准:1)多瘤病毒的基因组结构特点;2)多瘤病毒编码产物的生物学功能;3)多瘤病毒在转基因动物模型中的研究进展。根据纳入标准,符合分析的重要文献40篇。结果:多瘤病毒是小的环状闭合双链大约5 000bp的DNA病毒,包括早期编码区、晚期编码区和非编码调控区3个主要功能区。早期编码区通过选择性剪接形成大T抗原和小t抗原,大T抗原参与早晚期DNA的复制和转录调控,并与抑癌基因Rb和p53蛋白结合后使其失活,进而与多种恶性肿瘤发生关系密切。虽然SV40和JC病毒T抗原的序列同源性极高,但是大多数SV40T抗原转基因动物均可出现肿瘤,而JC病毒T抗原大多诱发出神经系统肿瘤,肿瘤的发生主要是由病毒T抗原的正确表达后完整存在决定的。结论:运用多瘤病毒T抗原建立恶性上皮肿瘤转基因动物研究不但可证实其与恶性上皮肿瘤的关系,也为揭示其致癌机制和上皮肿瘤的基因治疗提供重要手段。OBJECTIVE：To summarize genomic structure and its encoding product＇s functions of polyoma virus and the establishment of transgenic mice using polyoma oncogenie genes. METHODS： The papers were collected from PubMed database between 1990 and 2011 according to the key words：＂SV40 virus＂ OR ＂simian virus 40＂ OR ＂JC virus＂ OR ＂John Cunningham virus＂ OR ＂BK virus＂ （n 23 254） and selected in terms of the following criteria： l） The genomie DNA of polyomavirus;2） The biological function of polyomavirus encoding products; 3） Transgenic animal models induced by polyomavirus. According to the criteria, 40 papers were selected. RESULTS： Polyoma viruses have icosahedral caspids and contain small, circular and double-stranded DNA genomes,including early and late coding regions with a regulatory re- gion. The early region is alternatively spliced to produce large T antigen and small t antigen. T antigen can bind to and in- activate such tumor suppressors as p53 and pRb,which is closely linked to the tumorigenesis. Although there is high ho- mology between SV40 and JCV T antigen,the transgenic mice of SV40 T antigen exhibit various tumors and those of JCV T antigen induce the neural tumors in most cases,which is determined by the correct expression and whole existence of T antigen. CONCLUSIONS： It would be useful to establish transgenic animal of epithelial malignancies using polyoma virus T anti- gen, which can provide an evidence for its oncogenic role in the carcinogenesis. Additionally, the animal model would become a tool to investigate the molecular mechanisms of JCV oncogenesis and the approach of gene therapy for the cancer.

关 键 词：抗原 多瘤病毒转化 致癌物 模型 动物 综述文献 

分 类 号：R73-3[医药卫生—肿瘤]