title: BK virus as a cofactor in the etiology of prostate cancer in its early stages.
abstract: Prostate cancer has been projected to cause almost 10% of all male cancer deaths in the United States in 2007. The incidence of mutations in the tumor suppressor genes Rb1 and p53, especially in the early stages of the disease, is low compared to those for other cancers. This has led to the hypothesis that a human virus such as BK virus (BKV), which establishes a persistent subclinical infection in the urinary tract and encodes oncoproteins that interfere with these tumor suppressor pathways, is involved. Previously, we detected BKV DNA in the epithelial cells of benign and proliferative inflammatory atrophy ducts of cancerous prostate specimens. In the present report, we demonstrate that BKV is present at a much lower frequency in noncancerous prostates. Additionally, in normal prostates, T-antigen (TAg) expression is observed only in specimens harboring proliferative inflammatory atrophy and prostatic intraepithelial neoplasia. We further demonstrate that the p53 gene from atrophic cells expressing TAg is wild type, whereas tumor cells expressing detectable nuclear p53 contain a mix of wild-type and mutant p53 genes, suggesting that TAg may inactivate p53 in the atrophic cells. Our results point toward a role for BKV in early prostate cancer progression.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, 1500 E. Medical Center Dr., 6304 Cancer Center, SPC 5942, Ann Arbor, MI 48109-5942, USA.
authors.forename: Dweepanita
authors.initials: D
authors.lastname: Das
authors.forename: Kirk
authors.initials: K
authors.lastname: Wojno
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Imperiale
mesh_terms: D000230:Adenocarcinoma / Q000821:virology*; D001739:BK Virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D004279:DNA, Viral / Q000302:isolation & purification; D016158:Genes, p53; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D019913:Nuclear Localization Signals; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000821:virology*; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D019913:Nuclear Localization Signals