| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
We have previously reported that Runx3 is expressed by gastric epithelial cells, and that it is a major growth regulator of the cells. Analysis with human gastric cancer suggests that a lack of function of RUNX3 is causally related to the genesis and progression of human gastric cancer. We have also found evidence suggesting that loss of function of Runx3 may cause transdifferentiation of gastric epithelial cells into intestinal-type cells. These results suggest that Runx3 controls not only growth but also differentiation of gastric epithelial cells, and that it may play a key role in controlling intestinal metaplasia in the stomach.
In the present study, we tried to establish a culture system where gastric epithelial cells differentiate into intestinal-type cells. We found that some Runx3-knockout gastric epithelial cells did exhibit intestinal characteristics when they were cultured for more than 4 weeks on Matrigel. In such cases, gastric- and intestinal-type cells were intermingled with each other, suggesting that the differentiation of the gastric epithelial cells becomes unstable by the oss of Runx3, and that some gastric epithelial cells differentiated into intestinal-type cells by a stochastic mechanism.
These results demonstrate that gastric epithelial cells transdifferentiated into intestinal type. Using this culture system, we are now analyzing the molecular mechanism how gastric epithelial cells transdifferentiate into intestinal type cells to form intestinal metaplasia in the stomach, and also whether intestinal type cells trans-differentiated from gastric epithelial cells retain tumorigenic potencies, by transplanting the cells into nude mice, because it is widely believed that differentiated gastric tumors are derived from intestinal metaplasias, without any direct evidence.
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