| Project/Area Number |
16K15255
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Experimental pathology
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| Research Institution | Shinshu University |
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Principal Investigator |
Nakayama Jun 信州大学, 学術研究院医学系, 教授 (10221459)
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| Co-Investigator(Kenkyū-buntansha) |
春宮 覚 信州大学, 医学部, 助教(特定雇用) (50301792)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | A4gntノックアウトマウス / 糖鎖 / プロテオミクス / 分化型胃癌 / 膜結合型ムチン / αGlcNAc / 胃癌 / ノックアウトマウス |
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| Outline of Final Research Achievements |
Gastric gland mucin contains glycans carrying terminal α1,4-N-acetylglucosamine residues (αGlcNAc). A4gnt knockout (KO) mice spontaneously develop gastric adenocarcinoma, indicating thatαGlcNAc prevents gastric adenocarcinoma development. In this study, we performed proteomic analysis of proteins containing αGlcNAc that suppressed gastric cancer development. Mass spectrometric analysis of affinity purified proteins carrying αGlcNAc identified mucin core proteins, MUC6 and MUC5AC and mucin-related proteins, TFF2, gastrokine 2, and galectin 2. Furthermore, we identified the transmembrane glycoprotein mucin 1 (MUC1) as the protein carrying αGlcNAc. In addition, immunoblot and immunohistochemical analyses revealed that phosphorylation levels of STAT3, AKT, and ERK1/2 in gastric mucosa of A4gnt KO mice were significantly increased compared to those of wild type mice.
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| Academic Significance and Societal Importance of the Research Achievements |
胃粘膜下層に存在する腺粘液細胞は糖鎖の末端にα1,4結合したN-アセチルグルコサミン(αGlcNAc)を有し、A4gnt KOマウスの胃粘膜では分化型胃癌が自然発症する。このことからαGlcNAcは発癌シグナルを抑止している可能性がある。本研究では、αGlcNAc結合糖蛋白質を同定し、癌化に関連するシグナル伝達分子の性状を明らかにした。今後、これらの知見を発展させることにより、新たな胃癌の予防、治療法の開発へ繋がることが期待できる。
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