人脑肿瘤组织中SV40感染及其临床意义

目的 探讨猴病毒40（SV40）与人脑肿瘤发病的关系。方法 采用聚 一等奖反应（PCR）和原杂交（ISH）同时检测30例正常人脑组织和198例人及脑肿瘤组织以及SHG44和BT3 25两株人脑胶质瘤细胞系中SV40 DNA充列；并对SV40 DNA阳性肿瘤细胞采用免疫共沉淀和Western blot检测大T抗原（Tag）的表达及Tag-RB复合物的存在。结果 人脑肿瘤组织PCR SV40 DNA阳性率为48.5％（96／198），其中胶质瘤47.2％（42／89），脑膜瘤48.8％（21／43），脑垂体腺瘤51. 4%(18/35),神经鞘瘤43.8％（7／16），先天性肿瘤53.3％（8／15），正常人脑组织PCR SV40 DNA阳性率为6.7％（2／30）。SHG44及BT325两株细胞中也分别检测出SV40的DNA序列。人脑肿瘤组织SV40 DNA阳性率显著高于正常人脑组织（P＜0.01）。经ISH，仅在96例PCR SV40 DNA阳性的及脑肿瘤组织中检出87例阳性，2例SV40 DNA阳性的正常人脑组织中1例ISH阳性，SHG44及BT325两株细胞ISH SV40 DNA均阳性。SV40 DNA定位于肿瘤细胞核，阳性细胞呈弥温或片灶状分布。96人列SV40 DNA阳性脑瘤组织Tag表达阳性75例，所有Tag表达阳性瘤组织均发现Tag与RB形成特异性复合物。结论 人脑肿瘤组织中存在SV40感染，提示SV40感染与有脑肿瘤有关；在人脑肿瘤组织中Tag广泛表达，Tag可能是SV40在有禽肿瘤发生发展中起作用的重要因素，S V40 Tag与RB形成特异性复合物Tag-RB，导致RB活性，有是SV40致人脑肿瘤发生的一个重要机理。

The study of clinical significance of Simian virus 40 infection of human brain tumor tissues

Objective To study the infection of Simian Virus 40 (SV40) in human brain tumors and its potential role in the carcinogenesis of human brain tumors. Methods Polymerase chain reaction (PCR) and in situ hybridization (ISH) were used to detect SV40 DNA sequences from 198 samples of human brain tumor tissues as well as 30 normal brain tissues and two human glioma cell lines: SHG44 and BT325. Large tumor antigen (Tag) expression and Tag-RB complexes were investigated by immunoprecipitation and Western blot in SV40 DNA positive cases. Results SV40 DNA PCR were found in 48.5% (96/198) of human brain tumors, among which, SV40 DNA sequences were positive in 47.2% (42/89) gliomas, 48.8% (21/43) meningiomas, 51.4% (18/35) pituitary adenomas, 43.8% (7/16) neurilemomas, 53.3% (8/15) congenital tumors, 6.7% of normal brain tissues (2/30). SV40 DNA sequences were also found in SHG44 and BT325 cell lines. The positive rate of SV40 DNA in human brain tumors were significantly higher than that in human normal brain tissues (P<0.01). SV40 DNA were positive only in 87 human brain tumor tissues by ISH out of 96 SV40 DNA PCR positive cases, 1 out of 2 human normal brain tissues, and SHG44 and BT325 cell lines. Hybridization signals were identified in the nuclei of tumor cells and the positive cells distributed diffusively or focally. Tag expression was found in 75 human brain tumor tissues out of 96 SV40 DNA positive cases. Tag-RB specific complex was found in all of 75 Tag positive cases. Conclusions Human brain tumor tissues can be infected with SV40 and the infection is potentially correlated with human brain tumors. SV40 Tag was expressed highly in human brain tumor tissues, which might be an etiological agent in carcinogenesis of human brain tumors. SV40 Tag can form a specific complex with RB and the inactivation of RB due to the formation of Tag-RB complex may be an important mechanism in the pathogenesis of human brain tumors.