Role of Human Polyomavirus Bkv in Prostate Cancer

摘要

Prostate cancer has been predicted to cause nearly 10% of male cancer deaths in US in 2007. The frequency of mutations in the tumor suppressor genes (pRb and p53) is rare in prostate cancer. This has led to the possibility that a human virus like BK virus (BKV), which establishes a lifelong, subclinical persistent infection in the urinary tract and encodes oncoproteins (large T antigen, TAg; small T antigen, tAg), which interfere with these tumor suppressor pathways, may play a role in the early stages of the disease. Our initial analysis of cancerous prostate tissues shows the presence of BKV in normal and atrophic epithelium, which is a precursor lesion to prostate cancer and metastatic disease. TAg, which is a nuclear protein, is expressed in the atrophic cells, is cytoplasmic, and co-localizes with p53. We have extended our analysis to show that BKV is present at a much lower frequency in non-cancerous prostate. Additionally, TAg expression in normal prostate is only observed in specimens that have proliferative inflammatory atrophy and prostatic intraepithelial neoplasia. Utilizing laser capture microdissection, we observe an inverse correlation between TAg expression in atrophic epithelium and mutations in the p53 gene in those cells. This supports our hypothesis that BKV inactivates p53 in the early stages of prostate cancer. Our data suggests there could be a potential link between BKV and prostate cancer.