{"_buckets": {"deposit": "cd2549b4-8b68-4ede-924a-8960b1f252d9"}, "_deposit": {"created_by": 4, "id": "13031", "owners": [4], "pid": {"revision_id": 0, "type": "depid", "value": "13031"}, "status": "published"}, "_oai": {"id": "oai:gifu-pu.repo.nii.ac.jp:00013031", "sets": ["228"]}, "author_link": ["18205", "18203", "18204"], "item_1_biblio_info_14": {"attribute_name": "書誌情報", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2016-06-30", "bibliographicIssueDateType": "Issued"}, "bibliographicPageEnd": "10", "bibliographicPageStart": "1", "bibliographicVolumeNumber": "65", "bibliographic_titles": [{"bibliographic_title": "岐阜薬科大学紀要"}, {"bibliographic_title": "The annual proceedings of Gifu Pharmaceutical University", "bibliographic_titleLang": "en"}]}]}, "item_1_creator_6": {"attribute_name": "著者名(日)", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "五十里 , 彰"}], "nameIdentifiers": [{"nameIdentifier": "18203", "nameIdentifierScheme": "WEKO"}]}]}, "item_1_creator_7": {"attribute_name": "著者名よみ", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "イカリ, アキラ"}], "nameIdentifiers": [{"nameIdentifier": "18204", "nameIdentifierScheme": "WEKO"}]}]}, "item_1_creator_8": {"attribute_name": "著者名(英)", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "IKARI, Akira ", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "18205", "nameIdentifierScheme": "WEKO"}]}]}, "item_1_description_1": {"attribute_name": "ページ属性", "attribute_value_mlt": [{"subitem_description": "P(論文)", "subitem_description_type": "Other"}]}, "item_1_description_11": {"attribute_name": "抄録(日)", "attribute_value_mlt": [{"subitem_description": "肺がんによる死亡者数は増加傾向にあり、新たな治療標的の同定と治療法の開発が必要である。これまでに著者ら\nは、細胞間接着を構成するクローディン-2 が正常肺組織に発現しないが、腺がん組織に高発現することを見出している。\n肺腺がん細胞におけるクローディン-2 の発現をノックダウンすると細胞増殖能が低下したため、クローディン-2 による\n細胞増殖の調節機構を検討した。また、クローディン-2 が肺腺がんの治療標的になると考えられたため、クローディン-2\n発現を抑制する化合物を探索した。その結果、増殖期の細胞においてクローディン-2 は核内とタイトジャンクションに\n分布し、細胞周期調節因子のZO-1 associated nucleic acid binding protein（ZONAB）と結合することを解明した。クローデ\nィン-2 の発現をノックダウンすると、ZONAB の発現量が低下してG1 期の細胞の割合が増加した。クローディン-2 の核\n移行機序を検討し、208 番目のセリン残基のリン酸化が一部関与することを突き止めた。また、クローディン-2 指向性ペ\nプチドがタイトジャンクションから細胞質内へのクローディン-2 の移行を介してネクローシスによる細胞死を誘導する\nことを発見した。クローディン-2 はクラスリン依存性エンドサイトーシスによって細胞質内へ移行し、リソソームで分\n解された。フラボノイドのケルセチンはクローディン-2 の転写活性を低下させず、miR-16 マイクロRNA の発現誘導を介\nしてクローディン-2 mRNA 量の安定性を低下させ、その発現量を低下させた。クローディン-2 を起点とするがん化機構\nの解明とその阻害剤の探索は、肺腺がんの新たな治療法の開発につながると期待できる。", "subitem_description_type": "Other"}]}, "item_1_description_12": {"attribute_name": "抄録(英)", "attribute_value_mlt": [{"subitem_description": "The mortality associated with lung cancer has been increasing; consequently, novel therapeutic targets need to be\nidentified and novel therapeutic methods need to be developed. We recently reported that claudin-2, a component of the tight junction\n(TJ), was expressed in human lung adenocarcinoma, whereas it was absent from normal lung tissues. Knockdown of claudin-2 in\nlung adenocarcinoma cells decreased their proliferation. Therefore, we examined the mechanism underlying the regulation of cell\nproliferation by claudin-2. Moreover, we sought out compounds that can decrease claudin-2 expression. We found that claudin-2 was\ndistributed both in the nucleus and in the TJ in proliferating cells and was bound with the ZO-1 associated nucleic acid binding\n(ZONAB) protein, which controls cell-cycle regulator expression. shRNA-mediated knockdown of claudin-2 decreased ZONAB\nexpression and increased the proportion of cells in the G1 phase of the cell cycle. Moreover, we examined the nuclear trafficking of\nclaudin-2 and found that this trafficking was regulated in part by the phosphorylation of claudin-2 at Ser208. The short peptide,\nDFYSP, whose sequence mimics the second extracellular loop of claudin-2, caused claudin-2 to be trafficked from the TJ to cytosol,\nincreased lysosomal degradation of claudin-2, and induced necrotic cell death. Transport of claudin-2 to the cytosol was mediated via\na clathrin-dependent endocytosis pathway. Quercetin, a flavonoid, decreased claudin-2 expression through the induction of miR-16\nand a decrease in the stability of claudin-2 mRNA, although it did not inhibit the transcriptional activity of the claudin-2 gene. The\nclarification of the involvement of claudin-2 in the molecular mechanism underlying carcinogenesis and the identification of\nclaudin-2 inhibitors will lead to the development of novel agents for the treatment of lung adenocarcinoma.", "subitem_description_type": "Other"}]}, "item_1_source_id_13": {"attribute_name": "雑誌書誌ID", "attribute_value_mlt": [{"subitem_source_identifier": "AA1258935X", "subitem_source_identifier_type": "NCID"}]}, "item_1_text_10": {"attribute_name": "著者所属(英)", "attribute_value_mlt": [{"subitem_text_language": "en", "subitem_text_value": "Laboratory of Biochemistry, Gifu Pharmaceutical University"}]}, "item_1_text_2": {"attribute_name": "記事種別(日)", "attribute_value_mlt": [{"subitem_text_value": "総説"}]}, "item_1_text_3": {"attribute_name": "記事種別(英)", "attribute_value_mlt": [{"subitem_text_language": "en", "subitem_text_value": "Review"}]}, "item_1_text_9": {"attribute_name": "著者所属(日)", "attribute_value_mlt": [{"subitem_text_value": "岐阜薬科大学生命薬学大講座生化学研究室"}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2016-07-29"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "no65 2-11.pdf", "filesize": [{"value": "1.0 MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_11", "mimetype": "application/pdf", "size": 1000000.0, "url": {"label": "no65 2-11", "url": "https://gifu-pu.repo.nii.ac.jp/record/13031/files/no65 2-11.pdf"}, "version_id": "8c3be56a-4a96-417b-a068-b23045eecb8b"}]}, "item_keyword": {"attribute_name": "キーワード", "attribute_value_mlt": [{"subitem_subject": "肺がん", "subitem_subject_scheme": "Other"}, {"subitem_subject": "タイトジャンクション", "subitem_subject_scheme": "Other"}, {"subitem_subject": "クローディン", "subitem_subject_scheme": "Other"}, {"subitem_subject": "核移行", "subitem_subject_scheme": "Other"}, {"subitem_subject": "マイクロRNA", "subitem_subject_scheme": "Other"}, {"subitem_subject": "lung cancer", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}, {"subitem_subject": "tight junction", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}, {"subitem_subject": "claudin", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}, {"subitem_subject": "nuclear trafficking", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}, {"subitem_subject": "microRNA", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}]}, "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": "departmental bulletin paper", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "細胞間接着を起点とするがん化機構に関する研究", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "細胞間接着を起点とするがん化機構に関する研究"}, {"subitem_title": "Molecular Mechanism Underlying Carcinogenesis Caused by Abnormal Cell–cell Contact", "subitem_title_language": "en"}]}, "item_type_id": "1", "owner": "4", "path": ["228"], "permalink_uri": "https://gifu-pu.repo.nii.ac.jp/records/13031", "pubdate": {"attribute_name": "公開日", "attribute_value": "2016-07-29"}, "publish_date": "2016-07-29", "publish_status": "0", "recid": "13031", "relation": {}, "relation_version_is_last": true, "title": ["細胞間接着を起点とするがん化機構に関する研究"], "weko_shared_id": -1}