The oncogenic role of JC virus T antigen in lens tumors without cell specificity of alternative splicing of its intron

// Wen-feng Gou 1 , Shuang Zhao 1 , Dao-fu Shen 1 , Xue-feng Yang 1 , Yun-peng Liu 2 , Hong-zhi Sun 1 , Jun-sheng Luo 1 and Hua-chuan Zheng 1 1 Cancer Research Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, China 2 Department of Oncological Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China Correspondence to: Hua-chuan Zheng, email: // Keywords : JC virus, T antigen, oncogenesis, transgenic mouse, lens tumor Received : January 27, 2015 Accepted : February 01, 2015 Published : March 10, 2015 Abstract JC virus (JCV), a ubiquitous polyoma virus that commonly infects the human, is identified as the etiologic agent for progressive multifocal leukoencephalopathy and some malignancies. To clarify the oncogenic role of JCV T antigen, we established two transgenic mice of T antigen using either α-crystallin A (αAT) or cytokeratin 19(KT) promoter. Lens tumors were found in high-copy αAT mice with the immunopositivity of T antigen, p53, β-catenin and N-cadherin. Enlarged eyeballs were observed and tumor invaded into the brain by magnetic resonance imaging and hematoxylin-and-eosin staining. The overall survival time of homozygous mice was shorter than that of hemizygous mice (p<0.01), the latter than wild-type mice (p<0.01). The spontaneous salivary tumor and hepatocellular carcinoma were seen in αAT5 transgenic mice with no positivity of T antigen. KT7 mice suffered from lung tumor although JCV T antigen was strongly expressed in gastric epithelial cells. The alternative splicing of T antigen intron was detectable in the lens tumor of αAT mice, gastric mucosa of KT mice, and various cells transfected with pEGFP-N1-T antigen. It was suggested that JCV T antigen might induce carcinogenesis at a manner of cell specificity, which is not linked to alternative splicing of its intron. Both spontaneous lens and lung tumor models provide good tools to investigate the oncogenic role of JCV T antigen.