Runx3 controls growth and differentiation of gastric epithelial cells in mammals.
Runx3 is a transcription factor expressed by gastric epithelial cells. In the Runx3(-/-) mouse, gastric epithelia exhibited hyperplasia, and epithelial apoptosis was suppressed. By analyzing growth of the epithelial cells in primary culture, we found that Runx3(-/-) gastric epithelial cells are less sensitive to the growth-inhibitory and apoptosis-inducing activities of TGF-beta, suggesting that Runx3 is a major growth regulator of gastric epithelial cells by regulating their response to TGF-beta. We also found that Runx3 plays an important role in the control of gastric epithelial differentiation. When subcutaneously implanted into nude mice, Runx3(-/-) gastric epithelial cells formed tumors in which some cells differentiated into intestinal-type cells. Clonal analysis showed that gastric epithelial cells transdifferentiate into intestinal-type cells in the tumor. Considering that gastric epithelial differentiation is very stable, and that intestinal-type cells never differentiate in the mouse stomach, it is remarkable that gastric epithelial cells transdifferentiate into intestinal-type cells. We conclude that Runx3 is deeply involved in the control of both growth and differentiation of gastric epithelial cells. The role of Runx3 in the specification of gastric epithelial cells is discussed.
Fukamachi
Hiroshi
H
Department of Molecular Oncology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Tokyo 113-8519, Japan. hfukama.monc@tmd.ac.jp
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation / Q000235:genetics; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000502:physiology*; D005753:Gastric Mucosa / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development*; D007413:Intestinal Mucosa / Q000166:cytology; D051379:Mice; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D050677:Core Binding Factor Alpha 3 Subunit; C493730:Runx3 protein, mouse; D016212:Transforming Growth Factor beta