Activation of c-Myc and Cyclin D1 by JCV T-Antigen and beta-Catenin in Colon Cancer Article

Full Text via DOI: 10.1371/journal.pone.0106257 PMID: 25229241 Web of Science: 000342123900006
Open Access

Cited authors

  • Ripple, Michael J.; Struckhoff, Amanda Parker; Trillo-Tinoco, Jimena; Li, Li; Margolin, David A.; McGoey, Robin; Del Valle, Luis


  • During the last decade, mounting evidence has implicated the human neurotropic virus JC virus in the pathology of colon cancer. However, the mechanisms of JC virus-mediated oncogenesis are still not fully determined. One candidate to mediate these effects is the viral early transcriptional product T-Antigen, which has the ability to inactivate cell cycle regulatory proteins such as p53. In medulloblastomas, T-Antigen has been shown to bind the Wnt signaling pathway protein beta-catenin; however, the effects of this interaction on downstream cell cycle regulatory proteins remain unknown. In light of these observations, we investigated the association of T-Antigen and nuclear beta-catenin in colon cancer cases and the effects of this complex in the activation of the transcription and cell cycle regulators c-Myc and Cyclin D1 in vitro. Gene amplification demonstrated the presence of viral sequences in 82.4% of cases and we detected expression of T-Antigen in 64.6% of cases by immunohistochemistry. Further, we found that T-Antigen and beta-catenin co-localized in the nuclei of tumor cells and we confirmed the physical binding between these two proteins in vitro. The nuclear presence of T-Antigen and beta-catenin resulted in the significant enhancement of TCF-dependent promoter activity and activation of the b-catenin downstream targets, c-Myc and Cyclin D1. These observations provide further evidence for a role of JCV T-Antigen in the dysregulation of the Wnt signaling pathway and in the pathogenesis of colon cancer.

Publication date

  • 2014

Published in

International Standard Serial Number (ISSN)

  • 1932-6203


  • 9


  • 9