The role of Sox9 in the gastric carcinoma

• Project/Area Number: 16K09289
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Jichi Medical University
• Principal Investigator: Mutoh Hiroyuki 自治医科大学, 医学部, 教授 (50322392)
• Project Period (FY): 2016-10-21 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: Sox9 / 胃癌 / 腸上皮化生

Outline of Final Research Achievements

The gastric carcinoma is the 2nd cause of the death. The well-differentiated gastric carcinoma occurs from intestinal metaplasia generated by infection of Helicobacter pylori. But the gastric carcinoma also occurs after the eradication of Helicobacter pylori. It has been reported that the well-differentiated gastric carcinoma occurs from Cdx2-transgenic mice which generate intestinal metaplasia. The Sox9 located in the lower stream of the Wnt signal was also recognized in the intestinal metaplasia of Cdx2-Tg mice. It has been reported that Sox9 was also recognized in the human intestinal metaplasia and gastric carcinoma. To clarify the role of Sox 9 in the generation of gastric carcinoma, we generated the transgenic mice that express the Sox9 in the gastric mucosa. The gastric mucosa of Sox9-Tg mice was extremely thickened.

Academic Significance and Societal Importance of the Research Achievements

胃癌は死因の第2位である。分化型胃癌はピロリ菌の感染による腸上皮化生を基盤に発生する。しかしピロリ菌除菌後にも胃癌が発生する。腸上皮化生粘膜を発生するCdx2トランスジェニックマウスから分化型胃癌が発生することを報告してきた。Cdx2 Tgマウスの腸上皮化生粘膜ではWntシグナル下流に位置するSox9が発現していることも明らかにした。ヒトの腸上皮化生と分化型胃癌においてもSox9が発現していることを報告してきた。Sox9の胃癌発生における役割を明らかにするためSox9を胃粘膜に特異的発現するトランスジェニックマウスの作製に成功した。Sox9 Tgマウスの胃粘膜は著明に肥厚していた。