Khalili Kamel, Del Valle Luis, Otte Jessica, Weaver Michael, Gordon Jennifer
Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, 1900 North 12th Street, Philadelphia, PA 19122, USA.
Oncogene. 2003 Aug 11;22(33):5181-91. doi: 10.1038/sj.onc.1206559.
A number of recent studies have reported the detection of the ubiquitous human polyomavirus, JC virus (JCV), in samples derived from several types of neural as well as non-neural human tumors. The human neurotropic JCV was first identified as the etiologic agent of the fatal demyelinating disease, progressive multifocal leukoencephalopathy, which usually occurs in individuals with defects in cell-mediated immunity, including AIDS. However, upon mounting evidence of the oncogenic potential of the viral regulatory protein, T-antigen, and JCV's oncogenecity in a broad range of animal models, studies were initiated to determine its potential involvement in human carcinogenesis. Initially, the most frequently observed tumors in rodent models, including medulloblastoma, astrocytoma, glioblastoma, and other neural-origin tumors were analysed. These studies were followed by analysis of non-neural tumors such as colorectal carcinomas. In a subset of each tumor type examined, JC viral genomic DNA sequences could be detected by PCR and confirmed by Southern blot hybridization or direct sequencing. In a smaller subset of the tumors, the expression of T-antigen was observed by immunohistochemical analysis. Owing to the established functions of T-antigen including its ability to interact with tumor suppressor proteins such as Rb and p53, and its ability to influence chromosomal stability, potential mechanisms of JCV T-antigen-mediated cellular dysregulation are discussed. Further, as increasing evidence suggests that T-antigen is not required for maintenance of a transformed phenotype, a hit-and-run model for T-antigen-induced transformation is proposed.
最近的一些研究报告称，在源自几种类型的神经以及非神经人类肿瘤的样本中检测到了普遍存在的人类多瘤病毒——JC病毒（JCV）。嗜神经的人类JCV最初被确定为致命性脱髓鞘疾病——进行性多灶性白质脑病的病原体，该疾病通常发生在细胞介导免疫功能缺陷的个体中，包括艾滋病患者。然而，随着越来越多的证据表明病毒调节蛋白T抗原具有致癌潜力，并且JCV在广泛的动物模型中具有致癌性，人们开始开展研究以确定其在人类致癌过程中的潜在作用。最初，对啮齿动物模型中最常观察到的肿瘤进行了分析，包括髓母细胞瘤、星形细胞瘤、胶质母细胞瘤和其他神经源性肿瘤。随后对非神经肿瘤如结直肠癌进行了分析。在每种检查的肿瘤类型的一个子集中，可以通过PCR检测到JC病毒基因组DNA序列，并通过Southern印迹杂交或直接测序进行确认。在较小一部分肿瘤中，通过免疫组织化学分析观察到了T抗原的表达。由于T抗原已确定的功能，包括其与肿瘤抑制蛋白如Rb和p53相互作用的能力，以及其影响染色体稳定性的能力，因此讨论了JCV T抗原介导的细胞失调的潜在机制。此外，由于越来越多的证据表明维持转化表型不需要T抗原，因此提出了T抗原诱导转化的“Hit-and-Run”模型。
