Regulation of human neurotropic JCV in colon cancer cells.

Abstract

BACKGROUND: Recently, the genome of the human polyomavirus, JC (JCV), and expression of its early and late regulatory proteins (T-antigen and agnoprotein) have been demonstrated in neoplastic cells of colonic cancer cases. MATERIALS AND METHODS: Regulation of JCV was investigated in a human colon cancer cell line (SW480) and compared to a human glioblastoma cell line (U87-MG) that is permissive for JCV replication. RESULTS: SW480 cells supported basal transcription of both early and late JCV promoters. The expression of TCF-4, a component of Wnt signaling, modulated JCV transcription in a cell type-specific manner. Both TCF-4 and T-antigen bound to the JCV promoter region and bound to each other. In addition, the expression of TCF-4 caused a decrease in the ability of the T-antigen to stimulate viral DNA replication in U87-MG cells. CONCLUSION: Wnt pathway signaling proteins and T-antigen interact to regulate JCV in colonic epithelial cells.