Gastric carcinogenesis mechanism by impaired expression of Notch1 receptor through the deviation from cellular senescence

• Project/Area Number: 15K08946
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tohoku University
• Principal Investigator: Imatani Akira 東北大学, 医学系研究科, 教授 (30333876)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 胃癌 / エピジェネティック / Notch1 / 細胞老化 / 胃粘膜萎縮 / DNAメチル化 / Helicobacter

Outline of Final Research Achievements

Helicobacter pylori infection causes the differentiated gastric cancer through mucosal atrophy with aging. It is well known that Notch1 receptor regulates the maintenance of stem cells and its abnormality leads to the gastric carcinogenesis. In vitro analyses showed that the expression of Notch1 receptor was down-regulated through DNA methylation in human gastric cancer cells. And also, this study showed that restoration of its expression induced cellular senescence through the expression of p53, leading to the suppression of gastric tumorigenesis.