Dec. 2, 2002 An association between a common human virus and colon cancer has been established by a group of researchers from Temple University, suggesting a possible role for it in the development of cancer in the human intestinal tract.
Their study, "Association of Human Polyomavirus JCV with Colon Cancer: Evidence for Interaction of Viral T-Antigen and -catenin," appears in the Dec. 1 issue of Cancer Research.
Kamel Khalili, Ph.D., professor and director of Temple's Center for Neurovirology and Cancer Biology, and his co-investigators found the viral genome and viral proteins T-antigen and Agnoprotein in samples of malignant epithelial tumors in the large intestine, which may play a role in the development of the intestinal tract tumors.
"There is a human virus, called JC virus (JCV), which infects greater than 90 percent of the human population worldwide, usually during early childhood," says Khalili, the study's lead researcher.
According to Khalili, the JC virus most likely infects humans through the upper respiratory tract and remains in a latent stage in most people throughout their lives, and, in some cases, causes minor sub-clinical problems. However, in people whose immune systems are depressed, either through chemotherapy given to organ transplant recipients or an illness such as AIDS, JCV can become active and may contribute to cancer in the brain or cause the fatal demyelinating disease Progressive Multifocal Leukoencephalopathy (PML).
Khalili says that the current study suggests that, in addition to respiratory transmission, the virus may enter into the human population orally through contaminated food or water.
"What's interesting is that other studies have shown that this virus is present in raw sewage," says Khalili. "In fact, JC virus particles survive in the sewage. This suggests that we may get re-infected with the virus later on in life as well. Re-infection of the human population through contaminated water or food can take the virus into different organs, which in this case may be the intestinal tract. "
Khalili says that once in the intestinal tract, the genome of the JC virus expresses the viral protein T-antigen, which has oncogenic potential, and it associates with ß-catenin, an important protein for controlling cell division and balancing many of the normal biological events that occur in cells.
"ß-catenin's role in colon cancer has been previously suggested," says Khalili. "In this study, it seems T-antigen associates with ß-catenin and deregulates its function, and it's this deregulation that is causing induction of the tumors."
Khalili and the researchers used state-of-the-art laser micro-dissection to remove both cancerous and normal cells from the colon tissue and analyze them for JC virus genomic DNA.
Results from the gene amplification revealed the presence of the viral early genome in 22 of the 27 tumors sampled, and the expression of the viral proteins T-antigen and Agnoprotein was observed in more than 50 percent of the samples.
"Since its discovery almost 50 years ago, we thought that the JC virus was only expressed in cells of the nervous system," says Khalili.
"But in this study we are showing that the virus can also express its genes in non-neural tissue, which in this case is intestinal.
"What we show in this study, and our previous studies that showed an association between JCV and pediatric brain tumors, is that the JC virus has the ability to do more than just cause PML," adds Khalili, who has been studying the molecular biology of the JC virus for nearly two decades. "We have a virus in our body which may be involved in causing tumors."
Khalili says that the questions now facing researchers are whether or not the JC virus actually causes tumors; whether the tumors formed because of other elements and the virus helped as a co-factor; or whether something else causes the tumors and the presence of the virus is a mere coincidence.
"We're not saying every single tumor is being induced by the JC virus, because when you detect a virus in a tumor, you cannot actually say the virus causes it," Khalili cautions. "What we are stating is that the virus can be detected in a good number of the human colon cancer tumors we sampled, and the product of the virus, the viral protein T-antigen, which has oncogenic potential, can be detected in those tumor cells."
Khalili says that the discovery of the association between JCV and tumors is important for therapeutic and treatment reasons. "We can start developing strategies and vaccines against JC virus, which will hopefully lead to the prevention of the tumors it may induce," he says.
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