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- Title
Activation of c-Myc and Cyclin D1 by JCV T-Antigen and β-Catenin in Colon Cancer.
- Authors
Ripple, Michael J.; Parker Struckhoff, Amanda; Trillo-Tinoco, Jimena; Li, Li; Margolin, David A.; McGoey, Robin; Valle, Luis Del
- Abstract
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 β-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 β-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 β-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 β-catenin resulted in the significant enhancement of TCF-dependent promoter activity and activation of the β-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.
- Subjects
MYC oncogenes; CYCLINS; ANTIGEN analysis; CATENINS; COLON cancer; CARCINOGENESIS; JOHN Cunningham virus
- Publication
PLoS ONE, 2014, Vol 9, Issue 9, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0106257