September 21, 2005
Source: University of Guelph:
Research May Improve Knowledge of Colon Cancer
New research by University of Guelph scientists may lead to better understanding of the progression of colon cancer, one of the most common and deadly cancers.
The study headed by biomedical scientist Brenda Coomber, a professor in Guelph’s Ontario Veterinary College, is the cover story in the recent issue of Cancer Research, a prestigious international journal published by the American Association for Cancer Research.
Coomber, along with her research group in Guelph and scientists from McMaster University and the International Medical Centre of Japan, found a novel link among a genetic defect known as “mismatch repair,” the unstable environments that can surround cells, and gene mutation. Their findings may help scientists better understand why cellular mutations occur in colorectal cancer and may aid in the design of new therapies.
The researchers studied the mutation of the K-ras gene, one of the most common genetic alterations that contribute to cancer. The gene is an important player in normal cell function, Coomber said. “But when there is a mutation, it’s a dangerous thing, telling the cell to do things in an uncontrolled fashion. Once it starts, it’s like turning on a light switch that you cannot turn off.” It’s believed that this mutation is one of the causes of aggressive and continuous tumour growth in colon cancer.
The team concentrated on how the volatile environments that can surround cells — such as low levels of oxygen and nutrients — contribute to this mutation. It’s already well-established that unstable environments damage DNA, Coomber said. “But most studies assume that the DNA damage is what’s causing the mutation; our findings show it takes more than that.”
The researchers examined how different lines of cancer cells reacted in such environments, comparing cells that are “mismatch-repair deficient” with others. Normally, when DNA copies itself, the body has a system in check that identifies problems and makes gene repairs, Coomber said. “It’s sort of like a built-in spell checker that looks for errors and automatically corrects them.” In the case of mismatch repair defects, “the system is a sloppy proofreader,” she said.
The scientists discovered that unstable cellular environments seem to contribute to mutation of the K-ras gene by modulating mismatch repair. But volatile environments alone do not appear to be enough to trigger the gene mutation in cell lines that are not mismatch-deficient.
“We are hopeful that this research will give us a better idea of what might be going on with gene mutation and aid in increasing our knowledge of colon cancer,” Coomber said.
Collaborators on this study were U of G researchers Siranoush Shahrzad, Lindsay Quayle, Courtney Stone and Claire Plumb; Janusz Rak of McMaster’s Henderson Research Centre; and Japan’s Senji Shirasawa.
Prof. Brenda Coomber
Department of Biomedical Sciences
(519) 824-4120, Ext. 54922
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