Tumor suppressor activity of RUNX3.

Recent analyses have revealed that RUNX family members play important roles in both normal developmental processes and carcinogenesis. Of the three known RUNX family members, RUNX3 has been shown to be involved in neurogenesis of the dorsal root ganglia, T-cell differentiation and tumorigenesis of gastric epithelium. Deletion of the Runx3 locus in mice resulted in hyperplasia of the gastric epithelium due to the stimulation of proliferation and suppression of apoptosis that was accompanied by a reduced sensitivity to TGF-beta1. In primary human gastric cancer specimens, RUNX3 is frequently inactivated by allele loss or gene silencing due to promoter hypermethylation. The tumorigenicity of human gastric cancer cell lines in nude mice decreased as the level of RUNX3 expression increased, which indicates that RUNX3 is a bona fide tumor suppressor of gastric cancers.