Analysis of a mouse model of diffuse-type gastric cancer

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We have reported an E-cadherin/p53 double conditional knockout (DCKO) mouse line as the first genetically engineered diffuse-type gastric cancer (DGC), which recapitulates human DGC morphologically and molecularly. Recently, we have also established mouse DGC (MDGC) cell lines from primary tumors and lymph node metastases of the DCKO mice. We observed that the expression levels of epigenetic modulators and frequently methylated genes were up- and down-regulated in mouse primary DGC, respectively. Treatment with some epigenetic inhibitors induced differentiation and attenuated sphere formation of the MDGC cell lines in vitro. Moreover, we could validate tumor-suppressing activity of these agents in vivo. These results suggest that epigenetic alterations may play significant roles in diffuse-type gastric carcinogenesis and support to develop a relevant therapeutic strategy in human DGC.