| Budget Amount *help |
¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1999: ¥10,000,000 (Direct Cost: ¥10,000,000)
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| Research Abstract |
Because more than eighty percent of the familial colonic polyposis and sporadic colonic cancer are associated with mutations of the adenomatous polyposis coli gene (APC gene), APC gene was thought to participate in the pathogenesis of colonic cancer. On the other hand, non-steroidal anti-inflammatory drugs, which inhibit rate-limiting enzyme, cyclooxygenase-2, of the prostanoids biosynthesis, have been reported to inhibit the occurence and progression of coloic cancer. Moreover, the prostanoids have been reported to participate in the generation of the polyposis induced by azoxymethane. In this study, we intended to identify the prostanoid receptor participating in the generation of colonic cancer, and to clarify its mechanism to promote the carcinogenesis. We adopted two models to analyze the roles of the prostanoids on colonic calcinogenesis. One model is azoxymethane-induced carcinogenesis using the mice lacking each of the prostanoid receptor. The other is the model using the cross-breeding of the mice lacking each of the prostanoid receptor with mice lacking the APC gene product. Mice lacking the prostaglandin E receptor subtype EP1 showed decreased number and size of intestinal polyps when treated with azoxymethane. Moreover, mice lacking a prostaniod receptor cross-breeded with mice lacking the APC gene product had decreased number of intestinal polyps. These results show that some prostanoids via their cell-surface receptors play an immportant role in the carcinogenesis of the colon.
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