{"created":"2023-07-27T06:50:59.988727+00:00","id":44222,"links":{},"metadata":{"_buckets":{"deposit":"05e04e26-22cc-4f5e-9dc6-4981245ce31a"},"_deposit":{"created_by":18,"id":"44222","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"44222"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00044222","sets":["2812:2813:2827"]},"author_link":["73972","26701"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2007-04","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"4p.","bibliographicVolumeNumber":"2005-2006","bibliographic_titles":[{"bibliographic_title":"平成18(2006)年度 科学研究費補助金 基盤研究(B) 研究成果報告書"},{"bibliographic_title":"2006 Fiscal Year Final Research Report","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{},{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Wntシグナルの亢進は胃癌発生の重要な原因のひとつであると考えられている。また、胃癌組織では、プロスタグランジン合成酵素のCOX-2とプロスタグランジンE_2(PGE_2)変換酵素のmPGES-1の発現誘導も認められており、これらにより産生されるPGE2が胃癌発生に重要であると考えられている。しかし、WntシグナルとPGE_2経路の相互作用については不明な点が多かった。そこで、それぞれのシグナル経路を胃粘膜上皮で活性化させた2系統のトランスジェニックマウスを作製して交配実験を行ない、各シグナルの単独および相互作用による胃癌発生への影響について研究を行なった。\n胃粘膜上皮でWmtシグナルを活性化したK19-Wnt1マウスでは、未分化な上皮細胞のマーカーであるTFF2の陽性細胞数が増加し、細胞分化の抑制が認められた。また、このモデルでは胃粘膜に微小隆起病変が発生し、組織学的には異形性を伴う前癌病変であった。これらは、腫瘍形成には至らなかったので、Wntシグナル亢進は発癌の引き金になり得るが、それだけでは発癌に十分ではないと考えられた。一方、胃粘膜でPGE2産生を亢進したK19-C2mEマウスは、胃粘膜上皮でCOX-2とmPGES-1を同時に発現している。このマウスでは、粘液細胞化生をともなう過形成病変が認められた。すなわち、PGE2経路は細胞増殖の亢進と分化方向の制御に重要である可能性が考えられた。しかし、PGE2シグナル亢進だけでは異形性病変は発生しなかった。\n多くのヒト胃癌組織ではWntシグナルとPGE2経路の双方が亢進していると考えられるので、双方のマウスモデルを交配してダブルトランスジェニックマウス(K19-Wnt1/C2mE)を作製した。その結果、異形性を伴う胃癌発生が全ての個体で認められた。したがって、WntとPGE2の双方の活性化により胃癌が発生する事が明らかとなった。","subitem_description_type":"Abstract"},{"subitem_description":"Accumulating evidence indicates that the Wnt signaling as well as prostaglandin E_2 (PGE_2), a downstream product of cyclooxygenase 2 (COX-2), plays a key role in gastric tumorigenesis. However, the molecular mechanism remains poorly understood how the Wnt and PGE_2 pathways contribute to gastric tumorigenesis. To investigate their roles in gastric cancer, we have generated transgenic mice activating both pathways in the gastric epithelial cells, and examined their phenotypes. First, we constructed K19-C2mE mice that expressed COX-2 and mPGES-1 in the gastric mucosa using the keratin 19 (K19) promoter. mPGES-1 is a PGE_2 converting enzyme induced simultaneously with COX-2 in a variety of cancers. K19-C2mE mice showed mucous cell metaplasia and hyperplasia in the glandular stomach with heavy macrophage accumulation. Activation of mucosal macrophages and inflammatory response were responsible for metaplastic hyperplasia in K19-C2mE mice. We next constructed K19-Wntl transgenic mice expressing Wntl in the gastric mucosa under the control of K19 promoter. K19-Wntl mice had a significant suppression of epithelial differentiation, and developed small preneoplastic lesions consisting of undifferentiated epithelial cells with macrophage accumulation. However, K19-Wntl mice did not develop gastric tumors. We then crossed K19-Wnt1 mice with K19-C2mE to obtain K19-Wnt1/C2mE compound transgenic mice. Importantly, increase of PGE_2 through induction of COX-2 and mPGES-1 in the K19-Wnt1 mice converted the preneoplastic lesions into malignant gastric tumors. These results indicate that simultaneous activation of both Wnt and PGE_2 pathways causes malignant gastric tumors. Accordingly, K19-Wntl/C2mE mouse model is a useful, tool to study the genetic mechanism of gastric carcinogenesis through activation of the Wnt and PGE_2 pathways.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:17390114, 研究期間(年度):2005-2006","subitem_description_type":"Other"},{"subitem_description":"出典：「胃癌発生におけるWntシグナル亢進とCOX-2発現誘導の相互作用」研究成果報告書　課題番号17390114\n  (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)\n　　　本文データは著者版報告書より作成","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00050564","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学がん進展制御研究所"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=40324610","subitem_relation_type_select":"URI"}},{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390114/","subitem_relation_type_select":"URI"}},{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-17390114/173901142006kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2018-04-19"}],"displaytype":"detail","filename":"CA-PR-OSHIMA-M-kaken 2007-4p.pdf","filesize":[{"value":"150.3 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"CA-PR-OSHIMA-M-kaken 2007-4p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/44222/files/CA-PR-OSHIMA-M-kaken 2007-4p.pdf"},"version_id":"3cc2debd-e008-4c64-980c-1f44d7f5609a"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"胃癌発生におけるWntシグナル亢進とCOX-2発現誘導の相互作用","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"胃癌発生におけるWntシグナル亢進とCOX-2発現誘導の相互作用"},{"subitem_title":"Cooperation of Wnt signaling and COX-2 pathway in gastric carcinogenesis","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2827"],"pubdate":{"attribute_name":"公開日","attribute_value":"2018-04-19"},"publish_date":"2018-04-19","publish_status":"0","recid":"44222","relation_version_is_last":true,"title":["胃癌発生におけるWntシグナル亢進とCOX-2発現誘導の相互作用"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:34:23.280363+00:00"}