Scientists have identified a gene that appears to be intimately associated with the development and progression of stomach cancer. Researchers from South Korea and Japan report that the gene RunX3 functions as a strong tumor suppressor in normal cells and is frequently inactivated in many stomach cancers. Their findings are presented in today's edition of Cell.
Stomach cancer is the second most common cause of cancer-related mortality in the world and the most frequent malignancy of the gastrointestinal tract in Japanese and certain Southeast Asian populations. Forming an understanding of the mechanisms that underlie this disease has been an ongoing challenge for cancer biology.
Researchers, led by Dr. Suk-Chul Bae and Dr. Yoshiaki Ito, recently completed an intense series of experiments examining the RunX3 gene found in gastric epithelial cells, the cells that form the lining of the stomach. They engineered mice that were lacking functional RunX3 and found that suppression of this gene resulted in an overgrowth of gastric epithelial cells.
Even stimuli that are known to cause cell death were less effective on gastric cells from RunX3 negative mice, suggesting that RunX3 is a regulator of cell growth in gastric epithelial cells.
Given the critical role of RunX3 on gastric cell development, the authors went on to examine the role of RunX3 in human stomach cancer. RunX3 expression was reduced in 40% of early stage cancer cells and greater than 90% of late stage tumors.
According to Dr. Ito, “The evidence suggests that inactivation of RunX3 is important for the induction of gastric cancer as well as progression to a more malignant stage.”
The scientists found that in most cases of gastric cancer a biochemical alteration shut off gene function without actually altering the gene itself. The authors speculate that RunX3 reactivation is possible by chemically reversing the biochemical alterations that cause inhibition.
“Since reactivated RunX3 will be free of any mutations in most cases, reactivation of RunX3 means reactivation of the gene capable of inhibiting tumor growth strongly,” explained Dr. Ito. These results raise the possibility that chemical modification of silenced RunX3 may be an effective treatment for many stomach cancers.
[Contact: Dr. Suk-Chul Bae, Dr. Yoshiaki Ito]
05-Apr-2002
