| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Outline of Final Research Achievements |
Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a membrane-bound serine protease inhibitor expressed on epithelial and carcinoma cell surface. We have previously reported that HAI-1 KO mice showed significantly accelerated tumor formation in the intestine. This study aimed to analyze the roles for HAI-1 in intestinal carcinogenesis. To examine whether PAR-2 signaling is responsible for increased tumor formation observed with Hai-1 deficiency in the ApcMin+ model, we generated HAI-1,PAR-2 double KO mice. We observed that concomitant knockout of PAR-2 reduced the formation of intestinal tumors. Moreover, loss of PAR-2 alleviate the activation of NF-kB in the HAI-1 KO intestine. These results suggested that insufficient Hai-1 function induced PAR-2 activation. Excess activation of PAR-2 induces the activation of NF-kB signaling, which may be responsible for increased intestinal tumorigenesis.
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