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Induction of prostaglandin E2 pathway promotes gastric hamartoma development with suppression of bone morphogenetic protein signaling.
http://hdl.handle.net/2297/18176
http://hdl.handle.net/2297/18176d86e6f9d-b61b-4c1b-83f0-39d3c103f3fe
名前 / ファイル | ライセンス | アクション |
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CA-PR-OOSHIMA-H-2729.pdf (4.5 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2017-10-05 | |||||
タイトル | ||||||
タイトル | Induction of prostaglandin E2 pathway promotes gastric hamartoma development with suppression of bone morphogenetic protein signaling. | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Oshima, Hiroko
× Oshima, Hiroko× Itadani, Hiraku× Kotani, Hidehito× Taketo, Makoto Mark× Oshima, Masanobu |
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提供者所属 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 金沢大学がん研究所がん幹細胞研究センター | |||||
書誌情報 |
Cancer research 巻 69, 号 7, p. 2729-2733, 発行日 2009-04-01 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1538-7445 | |||||
NCID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA12004911 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1158/0008-5472.CAN-08-4394 | |||||
出版者 | ||||||
出版者 | American Association for Cancer Research | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Mutations in bone morphogenetic protein (BMP) receptor IA (BMPRlA) are responsible for a subset of cases of juvenile polyposis(JF) syndrome that develops hamartomatous tumors in the gastrointestinal tract. Mouse genetic studies have shown thatsuppression of BMP signaling in the intestines causes JP-type hamartoma development. Here, we generated K19-Nog transgenic miceexpressing noggin, a BMP antagonist, in gastric epithelium. However, inhibition of BMP signaling did not cause gastric phenotypes.We thus crossed K19-Nog with K19-C2mE mice that expressed Ptgs2 and Ptges in the stomach to generate compound transgenic mice. Expression of Ptgs2 and Ptges results in prostaglandin E2 (PGE2) biosynthesis, and both enzymes are induced in most human gastrointestinal tumors. Importantly, K19-Nog/ C2mE compound mice developed gastric hamartomas that were morphologicallysimilar to those found in JP with mucin-containing dilated cysts and inflammatory infiltration. Notably, treatment of K19-Nog/C2mE mice with a cyclo-oxygenase-2 inhibitor, celecoxib, significantly reduced tumor size with suppression of angiogenesis, suggesting that induction of the FGE2 pathway together with inhibition of BMP signaling is required for gastric hamartoma development.Moreover, microarray analyses revealed that canonical Wnt signaling target genes were not induced in K19-Nog/ C2mE hamartomas, indicating that BMP inhibition and PGE2 induction lead to gastric hamartoma development indepen- dent of the Wnt/ß-catenin pathway. These results, taken together, suggest that the FGE2 pathway is an effective preventive target against BMP-suppressed gastric hamartomas, as well as for Wnt/ß-catenin-activated adenocarcinomas. ©2009 American Association for Cancer Research. | |||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa |