Elucidation of the expression mechanism of the glycosyltransferase alpha4GnT that biosynthesizes the gastric adenocarcinoma suppressor alphaGlcNAc
| Project/Area Number |
17K17779
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Experimental pathology
Pathological medical chemistry
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| Research Institution | Shinshu University |
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Principal Investigator |
Komura Hitomi 信州大学, 医学部, 特任助教 (30616032)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | 胃癌 / 分化型腺癌 / αGlcNAc / α４GnT / A4gnt欠損マウス / マウス胎児 / α4GnT / 糖鎖 / 糖転移酵素 / 発癌 / 分化型胃癌 / 遺伝子発現 / MUC6 / Chst4 / 癌 / 細胞・組織 / 発現制御 / 発生・分化 |
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| Outline of Final Research Achievements |
Previously, we identified human α1, 4-N-acetylglucosaminyltransferase (α4GnT) that biosynthesizes O-glycans carrying terminal α1, 4-linked N-acetylglucosamine residues (αGlcNAc) in gastric mucosa, and engineered A4gnt -/- mice. A4gnt -/- mice showed complete lack of αGlcNAc expression in gastric gland mucin. Surprisingly, all the mutant mice developed gastric differentiated-type adenocarcinoma. This result suggests that αGlcNAc serves as a tumor suppressor for differentiated-type adenocarcinoma, but its detailed mechanism is unknown. 3-week-old A4gnt -/- mice develop gastric hyperplasia, so we considered that it is necessary to analyze the embryonic stomach in order to elucidate the carcinogenic mechanism. Therefore, we clarified the expression and localization of α4GnT and related molecules in the embryonic stomach of wild-type mice, and compared the results with that of A4gnt -/- mice to investigate the causal relationship with carcinogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
胃癌は分化型腺癌と未分化型腺癌に大別され、分化型腺癌は年齢とともにその罹患率が増加する。全てのA4gnt欠損マウスは、胃の幽門部に分化型腺癌が自然発症することから、分化型腺癌の有用なモデル動物であると考えられる。本研究は、野生型マウス胎児期のα4GnTおよびその関連分子の発現および局在を明らかにし、A4gnt欠損マウスにおけるその変化の様子を観察し、胃の分化型腺癌発症との因果関係を明らかにする。その結果は、腺癌に特化した胃癌発症メカニズムを理解し、胃癌に対する新しい予防法および治療法の確立に大きな道筋を開くものである。
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Report
(5 results)
Research Products
(4 results)
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[Journal Article] Analysis of A4gnt Knockout Mice Reveals an Essential Role for Gastric Sulfomucins in Preventing Gastritis Cystica Profunda2019
Author(s)
Masatomo Kawakubo, Hitomi Komura, Yukinobu Goso, Motohiro Okumura, Yoshiko Sato, Chifumi Fujii, Masaki Miyashita, Nobuhiko Arisaka, Satoru Harumiya, Kazuhiro Yamanoi, Shigenori Yamada, Shigeru Kakuta, Hiroto Kawashima, Michiko N Fukuda, Minoru Fukuda, Jun Nakayama
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Journal Title
J Histochem Cytochem
Volume: 67
Issue: 10
Pages: 759-770
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Cloning of Helicobacter suis cholesterol α-glucosyltransferase and production of an antibody capable of detecting it in formalin-fixed, paraffin-embedded gastric tissue sections,2017
Author(s)
Masatomo Kawakubo, Kazuki Horiuchi, Hitomi Komura, Yoshiko Sato, Masayoshi Kato, Meguru Ikeyama, Mana Fukushima, Shigenori Yamada, Satoshi Ishizone, Takehisa Matsumoto, Hiroyoshi Ota, Junji Sagara, Jun Nakayama
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Journal Title
Histochemistry and Cell Biology
Volume: 印刷中
Issue: 4
Pages: 463-471
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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