||The 2nd JSGE International Topic Conference Poster Session
The Role of Ral in Colitis-Associated Cancer in Mice
||Yoshino Takuya（Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Japan）
||Nakase Hiroshi（Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Japan）, Horiuchi Hisanori（Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Japan）, Chiba Tsutomu（Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Japan）
||Background：Patients with long-term IBD are at high risk of developing colitis-associated cancer（CAC）. The mechanisms of CAC were poorly understood. Small GTPase, Ral, is known to be highly activated in several human cancers, while how Ral activation contributes to CAC remains unclear. Aim：Our aim is to investigate the role of Ral in intestinal inflammation and CAC. Methods：In this study, we used Ral-GAP KO mice that could activate Ral in colon after inducting colitis.1）3% DSS was administrated to C57BL/6（WT）and Ral-GAP KO mice. After induction of colitis, we assessed survival rate and colonic inflammation. 2）Gene expressions of TNF-alpha, IL6 and IL17 in colonic tissues were evaluated. 3）We investigated whether Ral activation accelerated tumorigenesis in AOM/DSS model, in which Ral-GAP KO or WT mice received a single injection of AOM, followed by three rounds of DSS-colitis. Results：1）Colitis was significantly worsened in Ral-GAP KO mice with a 50% mortality rate compared to WT mice. 2）IL17 expression was significantly higher in Ral-GAP KO mice than WT mice, however, no significant difference of TNF-alpha and IL6 expression was observed. 3）Ral-GAP KO mice treated with AOM/DSS had invasive adenocarcinoma, while the tumor invasion was not observed in WT mice, in which tumors maintained a polypoid structure. Conclusion：Our data strongly suggests that Ral plays a critical role in the pathogenesis of CAC by enhancing tumor progression and IL17-related inflammation.