Runx3-/- gastric epithelial cells differentiate into intestinal type cells.
We have previously reported that Runx3, a runt domain transcription factor, is a major growth regulator of gastric epithelial cells, that a lack of RUNX3 function is causally related to the genesis and progression of human gastric cancer, and that expression of RUNX3 is greatly reduced in intestinal metaplasias in human stomachs. Here we examined the differentiation of Runx3-/- mouse gastric epithelial cells and found that some cells differentiated into intestinal type cells, which expressed Cdx2, a transcription factor that has been shown to induce intestinal metaplasia in transgenic mice. Differentiation of intestinal type cells was not found in culture of Runx3+/+ gastric epithelial cells. These results suggest that gastric epithelial cells can differentiate into intestinal type cells, probably due to expression of Cdx2 in them when the function of Runx3 is impaired. The relationship between loss of function of Runx3, formation of intestinal metaplasia, and gastric cancer was discussed.
Fukamachi
Hiroshi
H
Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan. h_fukama@biol.s.u-tokyo.ac.jp
Ito
Kosei
K
Ito
Yoshiaki
Y
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology*; D007413:Intestinal Mucosa / Q000166:cytology* / Q000473:pathology; D008679:Metaplasia; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins; C493730:Runx3 protein, mouse; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53