|Budget Amount *help
¥3,600,000 (Direct Cost : ¥3,600,000)
Fiscal Year 2006 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 2005 : ¥2,400,000 (Direct Cost : ¥2,400,000)
Helicobacter pylori (H.pylori) infection induces the 'switch of differentiation' from gastric oxytinc glands to atrophy and intestinal metaplasia(IM), which are a risk factor in gastric cancer development. This switch may be induced by host immune response to it. But little is known about the molecular mechanism of this 'switch of differentiation'. In this project, we have clarified one of the mechanisms through a homeobox gene Cdx2 and SRY-related HMG box gene Sox2. Cdx2, which can be developed IM, was induced by the H.pylori stimulation through phospho-AKT/AKT / NF-κB signaling pathway in gastric cell lines, AGS and GCIY. On the other hand, when stimulating with IFN-y, TNF-a, IL-1β and IL-4 in gastric cell lines, the expression level of Sox2 increased in both AGS and MKN45 after the stimulation with IL-4, a Th2-related cytokine, through STAT6 signaling. But little changes of Sox2 expression were observed after the treatment with IFN-γ, IL-1β, or TNF-a, Thl-related cytokine. Moreover, H. pylori infection and IFN-γ stimulation dose-dependently inhibited IL-4-induced expression of Sox2. The inhibition of Sox2 expression by siRNA transfection substantially increased the expression of Cdx2. Therefore, the down-regulation of Sox2 by H.pylori infection and Thl-dominant host immune response to it may promote gastric atrophy and intestinal metaplasia in the view of 'switch of differentiation'.