Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
J Med Virol. 2010 May;82(5):806-11. doi: 10.1002/jmv.21514.
Expression of the human polyomavirus JCV genome in several experimental animals induces a variety of neural origin tumors. The viral proteins, T-antigen and Agnoprotein, contribute to the oncogenesis of JCV by associating with several tumor suppressor proteins and dysregulating signaling pathways, which results in uncontrolled cell proliferation. In addition, T-antigen and Agnoprotein have been associated with DNA damage and interfering with DNA repair mechanisms. In this study, we have utilized commercially available tissue arrays of human tumors of various origins and demonstrated the expression of both T-antigen and Agnoprotein in some, but not all, tumors of neural and non-neural origin. Most notably, more than 40% of human glioblastomas and greater than 30% of colon adenocarcinomas express viral proteins. The detection of viral transforming proteins, T-antigen and Agnoprotein in the absence of viral capsid proteins suggests a role for JCV in the development and/or progression of human tumors. These results invite further large-scale investigation on the role of polyomaviruses, particularly JCV in the pathogenesis of human cancer.
人类多瘤病毒 JCV 基因组在几种实验动物中的表达会引发多种神经源性肿瘤。病毒蛋白 T 抗原和 Agnoprotein 通过与几种肿瘤抑制蛋白结合并扰乱信号通路，从而导致不受控制的细胞增殖，促进 JCV 的致癌作用。此外，T 抗原和 Agnoprotein 与 DNA 损伤有关，并干扰 DNA 修复机制。在这项研究中，我们利用了市售的各种来源的人类肿瘤组织芯片，并证明了 T 抗原和 Agnoprotein 在一些但不是所有神经源性和非神经源性来源的肿瘤中表达。值得注意的是，超过 40%的人脑胶质瘤和超过 30%的结肠腺癌表达病毒蛋白。在没有病毒衣壳蛋白的情况下检测到病毒转化蛋白 T 抗原和 Agnoprotein，提示 JCV 在人类肿瘤的发生和/或进展中发挥作用。这些结果邀请进一步对多瘤病毒（尤其是 JCV）在人类癌症发病机制中的作用进行大规模研究。
