{"created":"2023-07-27T06:44:29.925106+00:00","id":34744,"links":{},"metadata":{"_buckets":{"deposit":"7c0c5832-79ee-4942-8242-5a627d5bc4b1"},"_deposit":{"created_by":3,"id":"34744","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"34744"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00034744","sets":["2812:2813:2827"]},"author_link":["85765","245"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2007-04-01","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(C) 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":"肺癌におけるEGF receptorの異常とその下流因子の活性化 EGFR遺伝子の増幅と点突然変異、EGFR、Stat-3,Akt and Erk1/2の活性化(リン酸化)の関係を28例の肺癌を使って検討した。EGFRの増幅の見られた5例では、EGFR蛋白の発現のリン酸化の亢進、およびStat-3の活性化が認められた。点突然変異は5例にみられEGFR蛋白の発現のリン酸化の亢進があり、このうち4例ではAktの活性化があった。残りの19例中4例でEGFR蛋白の発現のリン酸化の亢進があったが、特定の下流因子の活性化との相関は見られなかった。しかしながら、Stat-3かAktのいずれかの活性化がみられた。以上の結果は、EGFR遺伝子の増幅によるEGFR蛋白の過剰発現ではStat-3が最も重要な活性化下流因子であることを示した。これに対し、EGFRの突然変異は恒常的にAkt系の活性化をもたらすと考えられた。またEGFR遺伝子の異常の多くは相反する下流因子の活性化をもたらすことが明らかになった。 骨軟部腫瘍におけるEGF receptorの異常とその下流因子の活性化 EGFR遺伝子の異常と下流因子の活性化〔リン酸化〕の関係を29例の骨軟部腫瘍について検索した。免疫染色では23%の肉腫にEGFRの過剰発現があり、このうち47%にEGFR蛋白のリン酸化の亢進が認められた。EGFR遺伝子の高度増幅のみられた悪性繊維性組織球腫の2例では蛋白の過剰発現と共にStat-3活性化がみられた。ミスセンス変異は3例にみられ、このうち2例でEGFRとStat-3の活性化があった。残りの症例でEGFRの過剰発現は見られたが、活性化は肉腫のみにみられた。3系の下流因子を比較すると、Stat-3やErk1/2に比べてAktの活性化の頻度が最も高く、Stat-3の活性化は上皮様性格を有する肉腫で頻度が高かった。 以上からEGFRの高度増幅→過剰発現ではStat-3の活性化が最も重要であり、EGFRの点突然変異ではかならずしも特定の下流因子の活性化と結びつかないと結論された。","subitem_description_type":"Abstract"},{"subitem_description":"The correlations among <I>EGFR</I> amplification, mutation, and activation of EGFR, Stat-3, Akt and Erk1/2 were investigated in 28 cases of human lung carcinomas. In 5 cases with <I>EGFR</I> amplification, EGFR expression and phosphorylation levels were higher, and Stat-3 was activated. Point mutations were detected in 5 cases, in which EGFR expression and phosphorylation were enhanced, and Akt was activated in 4 cases. In the remaining 19 cases, EGFR protein expression was upregulated and phosphorylated in 4 cases, but neither EGFR expression nor activation correlated with activation of particular downstream molecules. However, either Stat-3 or Akt, but not both, was activated reciprocally and complementarily. These results suggest that Stat-3 activation is a critical event downstream of overexpressed EGFR by gene amplifica tion. In contrast, tumor cells with <I>EGFR</I> mutation may persistently activate Akt-cascade. Finally, in the majority of cases without <I>EGFR</I> aberration, i ts downstream molecules function in reciprocal and complementary manner. The current data could provide novel insights into potential chemotherapeutic regimens for lung carcinomas, including inhibitors of Stat-3, Akt Correlations among EGFR aberrations and activation of proteins were investigated in 29 cases of bone/soft tissue tumors (BSTTs). By immunohistochemistry, EGFR overexpression was found in 22.6% of sarcomas. By immunoblotting, among sarcoma cases showing upregulation of EGFR, 47.4% showed EGFR activation. In 2 cases of MFH, with high level of EGFR copies, EGFR expression and phosphorylation levels were significantly higher, and Stat-3 was activated. Missense mutations were detected in 3 cases, and activation of EGFR and Stat-3 were found in 2 cases. In other cases, upregulation of the EGFR was found in both sarcomas and benign lesions, but activation was found only in sarcomas. Among the 3 downstream cascades, Akt pathway was most frequently activated than those of Stat-3 or Erkl/2,. and Stat-3 was activated in tumors exhibiting epithelial nature. These results suggest that Stat-3 activation may be a critical event downstream of overexpressed EGFR by high level EGFR copies. In contrast, EGFR mutation may not necessarily activate specific downstream cascades. These results suggest that EGFR-mediated cascades are candidates for molecular targeting therapy in defined subsets of BSTTs.","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:17590298, 研究期間(年度):2005–2006","subitem_description_type":"Other"},{"subitem_description":"出典：「ヒト固形癌におけるc-erbB-2およびEGFRのシグナル伝達系の解析」研究成果報告書　課題番号17590298\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":"10.24517/00034731","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学医学系研究科"}]},"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=50160411","subitem_relation_type_select":"URI"}},{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17590298/","subitem_relation_type_select":"URI"}},{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-17590298/175902982006kenkyu_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":"2017-10-05"}],"displaytype":"detail","filename":"ME-PR-OOI-A-kaken 2007-4p.pdf","filesize":[{"value":"143.1 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-OOI-A-kaken 2007-4p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/34744/files/ME-PR-OOI-A-kaken 2007-4p.pdf"},"version_id":"6844c8eb-8bea-424b-87f3-22986656aa51"}]},"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":"ヒト固形癌におけるc-erbB-2およびEGFRのシグナル伝達系の解析","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"ヒト固形癌におけるc-erbB-2およびEGFRのシグナル伝達系の解析"},{"subitem_title":"Analysis of the c-rtbB-2 and EGFR, and the ir downstream signal transduction system","subitem_title_language":"en"}]},"item_type_id":"9","owner":"3","path":["2827"],"pubdate":{"attribute_name":"公開日","attribute_value":"2017-10-05"},"publish_date":"2017-10-05","publish_status":"0","recid":"34744","relation_version_is_last":true,"title":["ヒト固形癌におけるc-erbB-2およびEGFRのシグナル伝達系の解析"],"weko_creator_id":"3","weko_shared_id":3},"updated":"2023-07-27T14:34:51.608677+00:00"}