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Association of Human Polyomavirus JCV with Colon Cancer

Evidence for Interaction of Viral T-Antigen and ß-Catenin¹

Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122 [S. E., L. D. V., C. L., D-D. G., K. K.]; Departmento de Patologia, The American British Cowdray Medical Center I. A. P., México D.F., México 01120 [C. O-H.]; and Department of Pathology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania 19107 [J. P. P.]

Infection of the gastrointestinal tract by the human polyomavirus, JCV, which has been frequently detected in raw urban sewage, can occur via intake of contaminated water and food. In light of earlier reports on the tumorigenecity of JCV, we investigated the presence of the JCV genome and the expression of viral proteins in a collection of 27 well-characterized epithelial malignant tumors of the large intestine. Results from gene amplification revealed the presence of the viral early genome in 22 of 27 samples. Expression of the viral oncogenic early protein, T-antigen, and the late auxiliary protein, Agnoprotein, was observed in >50% of the samples. The absence of the viral capsid protein in the tumor cells excludes productive replication of the virus in neoplastic cells. Laser capture microdissection confirmed the presence of the JCV genome and expression of T-antigen in precancerous villous adenomas and regions of invasive adenocarcinoma. The ability of JCV T-antigen to interact with ß-catenin and the nuclear detection of ß-catenin in T-antigen-positive cells suggests dysregulation of the Wnt pathway in the tumor cells. The coproduction of T-antigen and ß-catenin in colon cancer cells enhanced transcription of the c-myc promoter, the downstream target of ß-catenin. These observations provide evidence for a possible association of JCV with colon cancer and suggest a novel regulatory role for T-antigen in the deregulation of the Wnt signaling pathway through ß-catenin in tumors of the gastrointestinal tract.