Establishment of novel gastric cancer mouse models
Project/Area Number |
16K07111
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Tumor biology
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Research Institution | Kanazawa University |
Principal Investigator |
Oshima Hiroko 金沢大学, がん進展制御研究所, 准教授 (80362515)
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Research Collaborator |
Ida Miyuki
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 胃がん / 悪性化 / マウスモデル / 炎症とがん |
Outline of Final Research Achievements |
In this project, we tried to establish a new mouse model for gastric cancer with metastasis using Gan mice together with conditional gene knockout mice. First we constructed CreER expressing mice in the gastric mucosa using Claudin2 and Claudin18 promoter. Claudin2 expresses in the inflamed gastric epitherial cells and Claudin18 expresses in the normal gastric epithelia. Then, we crossed Gan mice that develop gastric tumors and Tgfbr2 conditional KO mice or p53 conditional KO mice together with Cldn18-CreERT2 mice. And these mice were treated with Tamoxifen. However, disruption of Tgfbr2 gene and additional p53 gene mutation did not cause any morphological changes or invasion phenotype of gastric tumors of Gan mice. These results indicate that TGF beta signaling and p53 mutation are not sufficient for gastric tumor malignant progression.
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Academic Significance and Societal Importance of the Research Achievements |
胃がんは、日本人で罹患率の高いがんであるため、胃がんの悪性化を模倣するマウスモデルの開発は、胃がんの死亡率の克服のために重要な課題である。今回の研究で、新規悪性化胃がんモデルマウスの開発には至らなかったが、大腸がんと異なり、TGF-beta遮断や変異型p53発現だけでは悪性化に至らないことを個体レベルで証明した。現在、胃がん悪性化に関与が示唆される遺伝子である、K-rasの変異を導入するマウスとの交配を行っている。また、炎症反応特異的に発現するCldn2遺伝子プロモーターを使ったCre発現マウスによって、炎症反応特異的にがん関連遺伝子を発現させることにより、悪性化マウスモデル開発が期待できる。
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Report
(4 results)
Research Products
(18 results)
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[Journal Article] Combined mutation of Apc, Kras and Tgfbr2 effectively drives metastasis of intestinal cancer.2018
Author(s)
Sakai E, Nakayama M, Oshima H, Kouyama Y, Niida A, Fujii S, Ochiai A, Nakayama KI, Minori K, Suzuki Y, Hong CP, Ock CY, Kim SJ, Oshima M.
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Journal Title
Cancer Res.
Volume: 78
Issue: 5
Pages: 1334-1346
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Intestinal cancer progression by mutant p53 through the acquisition of invasiveness associated with complex glandular formation.2017
Author(s)
Nakayama M, Sakai K, Echizen K, Yamada Y, Oshima H, Han TS, Ohki R, Fujii S, Ochiai A, Robine S, Voon DC, Tanaka T, Taketo MM, Oshima M.
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Journal Title
Oncogene
Volume: 36
Issue: 42
Pages: 5885-5896
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Myeloid Differentiation Factor 88 Signaling in Bone Marrow-Derived Cells Promotes Gastric Tumorigenesis by Generation of Inflammatory Microenvironment.2016
Author(s)
Maeda Y, Echizen K, Oshima H, Yu L, Sakulsak N, Hirose O, Yamada Y, Taniguchi T, Jenkins BJ, Saya H, Oshima M.
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Journal Title
Cancer prevention research
Volume: 9
Issue: 3
Pages: 253-263
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Novel oral transforming growth factor-β signaling inhibitor EW-7197 eradicates CML-initiating cells.2016
Author(s)
Naka K, Ishihara K, Jomen Y, Jin CH, Kim DH, Gu YK, Jeong ES, Li S, Krause DS, Kim DW, Bae E, Takihara Y, Hirao A, Oshima H, Oshima M, Ooshima A, Sheen YY, Kim SJ, Kim DK.
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Journal Title
Cancer Sci.
Volume: 107
Issue: 2
Pages: 140-148
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Book] リンパ学2017
Author(s)
大島浩子、越前佳奈恵、中山瑞穂、大島正伸
Total Pages
5
Publisher
日本リンパ学会
Related Report
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[Book] 特集 胃癌2017
Author(s)
大島浩子、越前佳奈恵、中山瑞穂、大島正伸
Total Pages
6
Publisher
日本臨床社
Related Report
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