Gene Reactivation May Inhibit Stomach Cancer

The RunX3 gene has been found to be a strong tumor suppressor in normal cells and is frequently inactivated in many stomach cancers. These findings were published in the April 5, 2002, issue 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.

Towards this end, Dr. Suk-Chul Bae of Chungbuk National University (Korea; www.chungbuk.ac.kr) and Dr. Yoshiaki Ito of Kyoto University (Japan) and their colleagues have been studying the RunX3 gene found in gastric epithelial cells, the cells that form the lining of the stomach. They genetically engineered a strain of mice that lacked functional RunX3 and found that suppression of this gene resulted in an overgrowth of gastric epithelial cells. Given the critical role of RunX3 on gastric cell development, the investigators went on to examine the role of RunX3 in human stomach cancer. RunX3 expression was reduced in 40% of early stage cancer cells and in more 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.”

In most cases of gastric cancer, a biochemical alteration shuts off gene function without actually altering the gene itself. Thus, it may be possible to chemically reverse the biochemical alterations that cause inhibition and reactivate RunX3 gene. "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.”







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Chungbuk National University
Kyoto University