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There is convincing evidence that Runx 3 is a new and important tumour suppressor in gastric cancer
In comparison with our knowledge of the detailed sequence of somatic genetic changes occurring during colon carcinogenesis, relatively few tumour suppressors or oncogenes have been commonly implicated during the multistage progression to cancer in the stomach. Now, in a collaborative venture reminiscent of their countries’ successful co-management of the 2002 World Cup, Li and 26 colleagues from South Korea and Japan have convincingly identified Runx 3 as a new and important tumour suppressor in gastric cancer.
Runx3/Pebp2alphaC null mouse gastric mucosa exhibits hyperplasias due to stimulated proliferation and suppressed apoptosis in epithelial cells, and the cells are resistant to growth-inhibitory and apoptosis-inducing action of TGF-beta, indicating that Runx3 is a major growth regulator of gastric epithelial cells. Between 45% and 60% of human gastric cancer cells do not significantly express RUNX3 due to hemizygous deletion and hypermethylation of the RUNX3 promoter region. Tumorigenicity of human gastric cancer cell lines in nude mice was inversely related to their level of RUNX3 expression, and a mutation (R122C) occurring within the conserved Runt domain abolished …