The oncogenic roles of John Cunningham virus T antigen in digestive epithelial cells with tissue specificity

Abstract: Background John Cunningham virus (JCV), a ubiquitous polyoma virus that commonly infects the human, is identified as the etiologic factor for progressive multifocal leukoencephalopathy and cancers. Methods Here, the transgenic mice of CAG-loxp-Laz-loxp T antigen were established and T antigen expression was especially activated in gastroenterological target cells with LacZ deletion using cre-loxp system. Results Gastric poorly-differentiated carcinoma was observed in T antigen-activated mice using K19-cre (stem-like cells) and PGC-cre (chief cells), but not Atp-4b-cre (parietal cells) or Capn8-cre (pit cells) mice. There appeared spontaneous hepatocellular and colorectal cancers in Alb-cre (hepatocytes)/T antigen and villin-cre (intestinal cells)/T antigen transgenic mice. Gastric, colorectal and breast cancer was observed in PGC-cre/T antigen mice. Pancreatic insulinoma and ductal adenocarcinoma, gastric adenoma, and duodenal cancer were detected in Pdx1-cre/T antigen mice. There was alternative splicing of T antigen mRNA in all target organs of these transgenic mice. Conclusions It was suggested that JCV T antigen might induce gastroenterological carcinogenesis at a manner of cell specificity. These spontaneous tumor models provide good tools to investigate the oncogenic role of T antigen in digestive cancers.