Activation of c-Myc and cyclin D1 by JCV T-Antigen and β-Catenin in colon cancer

Ripple, Michael J., Struckhoff, Amanda Parker, Trillo-Tinoco, Jimena, Li, Li, Margolin, David A., McGoey, Robin and Valle, Luis Del (2014) Activation of c-Myc and cyclin D1 by JCV T-Antigen and β-Catenin in colon cancer. PLos One, 9 9: . doi:10.1371/journal.pone.0106257


Author Ripple, Michael J.
Struckhoff, Amanda Parker
Trillo-Tinoco, Jimena
Li, Li
Margolin, David A.
McGoey, Robin
Valle, Luis Del
Title Activation of c-Myc and cyclin D1 by JCV T-Antigen and β-Catenin in colon cancer
Journal name PLos One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2014-09-17
Sub-type Article (original research)
DOI 10.1371/journal.pone.0106257
Open Access Status DOI
Volume 9
Issue 9
Total pages 11
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Formatted 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 b-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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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