Runx3 controls growth and differentiation of gastric epithelial cells in mammals
- PMID: 16466388
- DOI: 10.1111/j.1440-169X.2006.00832.x
Runx3 controls growth and differentiation of gastric epithelial cells in mammals
Abstract
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.
Similar articles
-
Growth regulation of gastric epithelial cells by Runx3.Oncogene. 2004 May 24;23(24):4330-5. doi: 10.1038/sj.onc.1207121. Oncogene. 2004. PMID: 15156189 Review.
-
Runx3-/- gastric epithelial cells differentiate into intestinal type cells.Biochem Biophys Res Commun. 2004 Aug 13;321(1):58-64. doi: 10.1016/j.bbrc.2004.06.099. Biochem Biophys Res Commun. 2004. PMID: 15358215
-
RUNX3 suppresses gastric epithelial cell growth by inducing p21(WAF1/Cip1) expression in cooperation with transforming growth factor {beta}-activated SMAD.Mol Cell Biol. 2005 Sep;25(18):8097-107. doi: 10.1128/MCB.25.18.8097-8107.2005. Mol Cell Biol. 2005. PMID: 16135801 Free PMC article.
-
Loss of RUNX3 expression correlates with differentiation, nodal metastasis, and poor prognosis of gastric cancer.Ann Surg Oncol. 2009 Jun;16(6):1686-94. doi: 10.1245/s10434-009-0428-2. Epub 2009 Mar 17. Ann Surg Oncol. 2009. PMID: 19290488
-
Tumor suppressor activity of RUNX3.Oncogene. 2004 May 24;23(24):4336-40. doi: 10.1038/sj.onc.1207286. Oncogene. 2004. PMID: 15156190 Review.
Cited by
-
DNA methylome of human neonatal umbilical cord: Enrichment of differentially methylated regions compared to umbilical cord blood DNA at transcription factor genes involved in body patterning and effects of maternal folate deficiency or children's sex.PLoS One. 2019 May 7;14(5):e0214307. doi: 10.1371/journal.pone.0214307. eCollection 2019. PLoS One. 2019. PMID: 31063509 Free PMC article.
-
RUNX family: Oncogenes or tumor suppressors (Review).Oncol Rep. 2019 Jul;42(1):3-19. doi: 10.3892/or.2019.7149. Epub 2019 May 6. Oncol Rep. 2019. PMID: 31059069 Free PMC article. Review.
-
miR-130a acts as a potential diagnostic biomarker and promotes gastric cancer migration, invasion and proliferation by targeting RUNX3.Oncol Rep. 2015 Sep;34(3):1153-61. doi: 10.3892/or.2015.4099. Epub 2015 Jul 1. Oncol Rep. 2015. PMID: 26134263 Free PMC article.
-
Molecular mechanisms of Barrett's esophagus.Dig Dis Sci. 2011 Dec;56(12):3405-20. doi: 10.1007/s10620-011-1885-6. Epub 2011 Oct 8. Dig Dis Sci. 2011. PMID: 21984436 Free PMC article. Review.
-
New insights into the inactivation of gastric tumor suppressor RUNX3: the role of H. pylori infection.J Cell Biochem. 2011 Feb;112(2):381-6. doi: 10.1002/jcb.22964. J Cell Biochem. 2011. PMID: 21268057 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
