The role of Notch/Hes1 signaling in the maintenance of homeostasis and carcinogenesis in pancreas

• Project/Area Number: 25461022
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyoto University
• Principal Investigator: Kodama Yuzo 京都大学, 医学(系)研究科(研究院), 助教 (80378687)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 膵癌 / Notchシグナル / Hes1 / 膵臓 / 前癌病変

Outline of Final Research Achievements

Pancreatic cancer is one of the most intractable cancers. It has been revealed that pancreatic cancer is derived from precancerous lesions by accumulation of multiple genetic abnormalities. Here, we focused on the Notch/Hes1 signaling in the maintenance of homeostasis and carcinogenesis in pancreas. As a result, we found that (1)Hes1 does not affect the cell fate of Ptf1a-positive cells, (2)Hes1 is indispensable for the development of pancreatic exocrine tissues after birth, (3)Hes1 is not essential for the maintenance of adult pancreatic homeostasis, (4)Hes1 is essential for the development of pancreatic precancerous lesions, (5) Hes1 is essential for the development of pancreatic cancer, and (6)the growth activities of pancreatic cancer cells were significantly diminished by a treatment of Hes1 inhibitor. These results suggest the possibility of a new therapeutic strategy against pancreatic cancer that targets Hes1.

Research Products

• [Journal Article] Pathogenicity of Immunoglobulin G in Patients with IgG4-related Disease. (2016)
  • Author(s): Shiokawa M, Kodama Y, Kuriyama K, Yoshimura K, Tomono T, Morita T, Kakiuchi N, Matsumori T, Mima A, Nishikawa Y, Ueda T, Tsuda M, Yamauchi Y, Minami R, Sakuma Y, Ota Y, Maruno T, Kurita A, Sawai Y, Tsuji Y, Uza N, Matsumura K, Watanabe T, Notohara K, Tsuruyama T, Seno H, Chiba T.
  • Journal Title: Gut Volume: 未定 Issue: 8 Pages: 3292-3301
  • DOI: 10.1136/gutjnl-2015-310336
  • Peer Reviewed / Acknowledgement Compliant