Association of human polyomavirus JCV with colon cancer: evidence for interaction of viral T-antigen and beta-catenin.
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 beta-catenin and the nuclear detection of beta-catenin in T-antigen-positive cells suggests dysregulation of the Wnt pathway in the tumor cells. The coproduction of T-antigen and beta-catenin in colon cancer cells enhanced transcription of the c-myc promoter, the downstream target of beta-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 beta-catenin in tumors of the gastrointestinal tract.
Enam
Sahnila
S
Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122, USA.
Del Valle
Luis
L
Lara
César
C
Gan
Dai-Di
DD
Ortiz-Hidalgo
Carlos
C
Palazzo
Juan P
JP
Khalili
Kamel
K
D000230:Adenocarcinoma / Q000821:virology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000957:Antigens, Viral, Tumor / Q000096:biosynthesis*; D003110:Colonic Neoplasms / Q000378:metabolism / Q000821:virology*; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007577:JC Virus / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D027601:Polyomavirus Infections / Q000150:complications* / Q000821:virology; D015534:Trans-Activators / Q000096:biosynthesis*; D014412:Tumor Virus Infections / Q000150:complications* / Q000821:virology; D051176:beta Catenin
D000957:Antigens, Viral, Tumor; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin