disease, only a handful of scientists are studying a possible connection to cancer.
Polyomaviruses have very small genomes, and they dont have the genes required to copy their own DNA, says Dweepanita Das, PhD, a U-M post-doctoral fellow and first author on the paper. The virus must induce its host cell to divide, so it can use the cells genes to make proteins the virus needs to reproduce. BK virus uses a protein called T antigen, or TAg, to induce cell division. The problem is that when you interrupt the normal cell cycle to force a cell to divide, sometimes the cell continues to divide abnormally.
U-M scientists analyzed 21 samples of prostate tissue from men with adenocarcinoma whose prostates were surgically removed to prevent the spread of cancer. Tissue samples were obtained from the Tissue Procurement Core at the U-Ms
Using new TAg-specific protein assays they developed, the research team searched the tissue to identify cells containing TAg. Scientists also removed DNA from the prostate tissue samples for sequencing and identification in the U-Ms DNA Sequencing Core facility.
The results showed that 71 percent of the prostate samples analyzed for the study contained gene segments from the BK virus. TAg protein from the BK virus was present in 43 percent of the tissue samples, but only in atrophic lesions a precursor stage of prostate cancer development. TAg was not expressed in normal cells or cancerous cells.
Atrophic lesions comprise a spectrum of architectural and cytological differences in the appearance of epithelial cells lining the glands in the prostate, says Rajal B. Shah, MD, MBBS, a clinical assistant professor of pathology and urology in the
In addition to TAg protein, atrophic lesions also contained high levels of protein expressed by the p53 tumor suppressor gene. When U-M scientists discovered that TAg and p53 proteins were located together in the cytoplasm of atrophic lesion cells, but not in the nucleus, an important piece of the puzzle fell into place.
We know that for p53 to function as a tumor suppressor gene, its protein product must be in the cells nucleus, explains Imperiale. TAg apparently sequesters p53 protein in the cells cytoplasm, preventing it from entering the nucleus and giving the signal for the cell to stop dividing and die.
Imperiales working hypothesis is that the BK virus infects epithelial cells in the prostate and transforms them into atrophic lesions through TAg expression. This produces an area of uncontrolled cell growth, which if circumstances are right can eventually develop into prostate cancer.
If hes right, prostate cancer may have something in common with cervical cancer, which is caused by a different virus the human papillomavirus.
Papillomavirus makes proteins with the same function as T antigen, Imperiale says. They induce cell growth and inactivate the p53 gene, preventing it from killing abnormal cells. So, its a logical possibility that a similar mechanism occurs in at least some cases of prostate cancer, but much additional research will be needed before we can know for sure.
The U-M study was funded by a grant from the U.S. Armys Medical Research and Material Command, Department of Defense.