Expression of human neurotropic polyomavirus JCV late gene product agnoprotein in human medulloblastoma
Expression of human neurotropic polyomavirus JCV late gene product agnoprotein in human medulloblastoma
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DOI：
10.1093/jnci/94.4.267
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发表时间：
2002-02-20
影响因子：
10.3
通讯作者：
Khalili, K
中科院分区：
文献类型：
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作者：
Del Valle, L;Gordon, J;Khalili, K
背景人类嗜神经性多瘤病毒（JCV）在病毒基因组的晚期区域内含有一个开放阅读框，编码一种71个氨基酸的蛋白质，即未知蛋白。由于越来越多的证据支持JCV感染和人类脑肿瘤（包括髓母细胞瘤）之间的关联，我们评估了一系列20例特征明确的髓母细胞瘤中JCV阿尼奥基因序列的存在和Agnoprotein的表达。方法：采用福尔马林固定、石蜡包埋的肿瘤组织标本进行阿尼奥基因扩增和免疫组化分析。相邻切片用抗未知蛋白的抗体和抗细胞结构和调节蛋白的抗体染色，包括JCV早期基因产物T抗原。结果：对石蜡包埋样本的扩增DNA分析显示，16份样本中有11份（69%）存在阿尼奥基因。免疫组化分析显示，在20个样本中的11个（55%）的肿瘤细胞胞浆定位和广泛分布的未知蛋白。JCV早期基因产物T抗原存在于部分（但不是全部）肿瘤细胞的细胞核中。一些髓母细胞瘤样本，表达未知蛋白没有T抗原表达的迹象。p53仅在11个表达未知蛋白的肿瘤中的6个中检测到。20个样品中没有一个显示病毒晚期衣壳蛋白的表达，排除了JCV对肿瘤细胞的生产性感染。结论：我们的数据提供了证据，JCV晚期基因编码的辅助未知蛋白在肿瘤细胞中表达。在缺乏T抗原表达的情况下发现未知蛋白的表达提示未知蛋白在参与JCV相关髓母细胞瘤发展的途径中的潜在作用。
Background. The human neurotropic polyomavirus, JCV, contains an open reading frame within the late region of the viral genome that encodes a 71-amino-acid protein, agnoprotein. Because accumulating evidence supports an association between JCV infection and human brain tumors, including medulloblastomas, we assessed the presence of JCV Agno gene sequences and the expression of agnoprotein in a series of 20 well-characterized medulloblastomas. Methods: Formalin-fixed, paraffin-embedded tumor tissue samples were used for Agno gene amplification and for immunohistochemical analysis. Adjacent sections were stained with an antibody to agnoprotein and with antibodies to cellular structural and regulatory proteins, including the JCV early gene product, T antigen. Results: Analysis of amplified DNA from paraffin-embedded samples revealed the presence of the Agno gene in 11 (69%) of 16 samples. Immunohistochemical analysis showed cytoplasmic localization and widespread distribution of agnoprotein in the neoplastic cells in 11 (55%) of 20 samples. The JCV early gene product, T antigen, was present in the nucleus of some, but not all, of the neoplastic cells. Some medulloblastoma samples that expressed agnoprotein had no sign of T-antigen expression. p53 was detected in only six of the 11 tumors in which agnoprotein was expressed. None of the 20 samples showed expression of the viral late capsid proteins, ruling out productive infection of the tumor cells with JCV. Conclusions: Our data provide evidence that the JCV late gene encoding the auxiliary agnoprotein is expressed in tumor cells. The finding of agnoprotein expression in the absence of T-antigen expression suggests a potential role for agnoprotein in pathways involved in the development of JCV-associated medulloblastomas.