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By Merritt McKinney
NEW YORK, Mar 22 (Reuters Health) - Researchers seeking to unravel the workings of a gene involved in many cases of colon cancer may have discovered a way to target it for therapy, according to a new report. The gene is called APC (adenomatous polyposis coli), and it normally acts as a tumor suppressor. Mutations in the gene can be inherited or occur randomly.
Now new research, published in two reports in the April issue of the journal Nature Cell Biology, sheds light on exactly how the APC gene may lead to colon cancer. It seems that the gene mutations may lead to chromosome instability--a situation that causes some cells to have too many chromosomes and others to not have enough. An abnormal chromosome number, which generally occurs when the cell is dividing, is a common characteristic of cancer cells.
Colorectal tumors with chromosome instability have a poor prognosis, according to Dr. Riccardo Fodde, of Leiden University in the Netherlands, who is a co-author of one of the reports. But the cause of this instability has been unknown, he told Reuters Health.
Based on experiments using cells from mouse embryos, the researchers found that APC normally plays a role in regulating chromosome stability by making sure that the right number of chromosomes appear in each newly divided cell. But stem cells with defective APC genes displayed extensive chromosome instability in the experiments.
Another set of researchers also detected a link between mutations in APC and chromosome instability. Dr. Inke S. Nathke, of the University of Dundee in the UK, and colleagues detected extensive chromosome instability in embryonic stem cells that had a shortened version of the APC gene.
"The importance of our work is that it provides the first molecular link between chromosome instability and the APC protein that is very commonly mutated in colon cancer, especially in the very early stages," Nathke told Reuters Health.
"Our results point to one of the crucial functions (of APC) that therapy should aim to restore," she continued.
"This is exciting because changes in APC appear very early in the progression to colon cancer," Nathke noted. "Reversing changes induced by loss of normal APC early by targeting the most vital mechanism could prevent malignant colon cancer in patients." Such an approach would be especially useful in patients with hereditary colon cancer caused by mutations in APC, according to Nathke.
SOURCE: Nature Cell Biology 2001;3:429-438.
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