Comment on Levanon et al., "Runx3 knockouts and stomach cancer", in EMBO reports (June 2003).

correspondence correspondence 538 I n this issue, Y. Groner and colleagues discuss the possible involvement of the transcription factor Runx3 in stomach cancer (Concept, pp.560–564). The fundamental point of the article is that, although both of our groups observed the same neurological and T-cell phenotypes in Runx3 knockout (KO) mice, the C57BL6 strain that we used (type I KO; Li et al., 2002) developed gastric abnormalities , whereas the ICR strain used by Groner (type II KO; Levanon et al., 2002) did not. Although careful analysis to find reasons for the differences in these studies is necessary, we feel that important points were not made in this Concept and need to be addressed here. We acknowledged the differences between the two strains in one of our subsequent papers (Inoue et al., 2002), but as the ICR strain is outbred, we did not further analyse its phenotype. However, we have shown that Runx3 is involved in the transforming growth factor-β (TGF-β) signalling pathway, and it is well known that responses to TGF-β vary in different strains of mice (Kallapur et al., 1999), which could explain the difference in the gastric phenotypes of the type I and type II KO mice. The other main query raised over the use of the C57BL6 mice was that they are more susceptible to Helicobacter felis infection. However, we examined the stomach epithelium of Runx3 –/– C57BL6 mice before the mice drank milk, ruling out the possibility of Helicobacter involvement in the phenotype we described. Groner's group was unable to detect the Runx3 protein in the gastric epithelium of mouse embryos and therefore question whether the gastric abnormalities seen in the type I KO mice are due to a lack of Runx3. On the basis of their results, they conclude that Runx3 is not expressed in mouse stomach epithelial cells at any time during their life cycle. This is the most direct contradiction between the two groups and therefore merits careful investigation. Genes involved in development and differentiation, such as the Runx genes, change their expression patterns during development. We have shown that Runx3 is expressed in the glandular stomach epithelial cells of 10-week-old mice and also in the embryonic epithelial cells, albeit at much lower levels (Li et al., 2002). Thus, the levels at this early stage might have been too low to be detected in Groner's study. Importantly, specific anti-bodies were used for detection …