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Cisplatin has been used as a key drug in the treatment for patients with lung cancer; however, most of the patients failed to respond to cisplatin within several months, and the mechanisms underlying the cisplatin resistance have not been fully elucidated. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is a key adaptor protein in the formation of inflammasomes. ASC is also involved in apoptotic signaling. Importantly, ASC expression is decreased in lung cancer and various cancers, but its precise function in tumor progression remains unknown. To explore the hitherto unknown role of ASC in lung cancer, we initially searched for lung cancer cell lines with higher expression levels of ASC using Cancer Cell Line Encyclopedia (CCLE) database, thereby identifying the A549 human non-small cell lung cancer cell line. Accordingly, with retroviral shRNA, the expression of ASC was forced to decrease in A549 cells. Stable ASC-knockdown cells, thus established, showed the increased activities of proliferation, motility, and invasion, compared with control cells. Importantly, ASC-knockdown cells also became resistant to cisplatin, but not to other anti-cancer agents, 5-fluorouracil and paclitaxel. Bcl-2 and phospho-Src levels were increased in ASC-knockdown cells. A Bcl-2 inhibitor, ABT-199, induced an apoptotic response in ASC-knockdown cells, and dasatinib, a Src inhibitor, blocked cell invasiveness. Thus, ASC may be involved in tumor suppression and cell death via Bcl-2 and pSrc. Targeting BcI-2 and Src in ASC-downregulated populations of lung cancer may improve treatment outcome."}]}, "item_1627890986942": {"attribute_name": "出版タイプ", "attribute_value_mlt": [{"subitem_version_resource": "http://purl.org/coar/version/c_be7fb7dd8ff6fe43", "subitem_version_type": "NA"}]}, "item_access_right": {"attribute_name": "アクセス権", "attribute_value_mlt": [{"subitem_access_right": "open access", "subitem_access_right_uri": "http://purl.org/coar/access_right/c_abf2"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "境澤, 隆夫", "creatorNameLang": "ja"}], "nameIdentifiers": [{"nameIdentifier": "108054", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2019-06-13"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "13MH206D_yoshi.pdf", "filesize": [{"value": "85.0 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 85000.0, "url": {"label": "内容の要旨", "url": "https://soar-ir.repo.nii.ac.jp/record/20718/files/13MH206D_yoshi.pdf"}, "version_id": "8971c016-3e44-48ae-ad4b-373a3545da1f"}, {"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2019-06-13"}], "displaytype": "detail", "download_preview_message": "", "file_order": 1, "filename": "13MH206D_shinsa.pdf", "filesize": [{"value": "121.2 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 121200.0, "url": {"label": "審査結果の要旨", "url": "https://soar-ir.repo.nii.ac.jp/record/20718/files/13MH206D_shinsa.pdf"}, "version_id": "ac3d0878-d3b4-48c2-9ca6-fe101e8a2ae9"}, {"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2019-06-13"}], "displaytype": "detail", "download_preview_message": "", "file_order": 2, "filename": "13MH206D_ronbun.pdf", "filesize": [{"value": "794.1 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensefree": "© 2018 Tohoku University Medical Press", "licensetype": "license_note", "mimetype": "application/pdf", "size": 794100.0, "url": {"label": "博士論文の全文", "objectType": "fulltext", "url": "https://soar-ir.repo.nii.ac.jp/record/20718/files/13MH206D_ronbun.pdf"}, "version_id": "0cb29cda-a993-4e52-865c-d142cd6d1d82"}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "doctoral thesis", "resourceuri": "http://purl.org/coar/resource_type/c_db06"}]}, "item_title": "Potential Roles of ASC, a Proapoptotic Protein, for Determining the Cisplatin Susceptibility of Lung Cancer Cells(アポトーシス促進性蛋白質であるASCは肺癌細胞のシスプラチン感受性を決定する役割を担う)", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Potential Roles of ASC, a Proapoptotic Protein, for Determining the Cisplatin Susceptibility of Lung Cancer Cells(アポトーシス促進性蛋白質であるASCは肺癌細胞のシスプラチン感受性を決定する役割を担う)", "subitem_title_language": "en"}]}, "item_type_id": "14", "owner": "1", "path": ["849"], "permalink_uri": "http://hdl.handle.net/10091/00021476", "pubdate": {"attribute_name": "PubDate", "attribute_value": "2019-06-14"}, "publish_date": "2019-06-14", "publish_status": "0", "recid": "20718", "relation": {}, "relation_version_is_last": true, "title": ["Potential Roles of ASC, a Proapoptotic Protein, for Determining the Cisplatin Susceptibility of Lung Cancer Cells(アポトーシス促進性蛋白質であるASCは肺癌細胞のシスプラチン感受性を決定する役割を担う)"], "weko_shared_id": -1}
Potential Roles of ASC, a Proapoptotic Protein, for Determining the Cisplatin Susceptibility of Lung Cancer Cells(アポトーシス促進性蛋白質であるASCは肺癌細胞のシスプラチン感受性を決定する役割を担う)
http://hdl.handle.net/10091/00021476
http://hdl.handle.net/10091/000214760eed29ea-dce3-4e6b-a365-621e284f74e2
名前 / ファイル | ライセンス | アクション |
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2019-06-14 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Potential Roles of ASC, a Proapoptotic Protein, for Determining the Cisplatin Susceptibility of Lung Cancer Cells(アポトーシス促進性蛋白質であるASCは肺癌細胞のシスプラチン感受性を決定する役割を担う) | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_db06 | |||||
タイプ | doctoral thesis | |||||
アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
著者 |
境澤, 隆夫
× 境澤, 隆夫 |
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出版者 | ||||||
出版者 | 信州大学 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 境澤 隆夫. Potential Roles of ASC, a Proapoptotic Protein, for Determining the Cisplatin Susceptibility of Lung Cancer Cells(アポトーシス促進性蛋白質であるASCは肺癌細胞のシスプラチン感受性を決定する役割を担う). 信州大学, 2018, 博士論文. | |||||
書誌情報 |
発行日 2018-03-31 |
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学位授与番号 | ||||||
学位授与番号 | 13601甲第1135号 | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2018-03-31 | |||||
学位名 | ||||||
学位名 | 博士(医学) | |||||
学位授与機関 | ||||||
学位授与機関識別子Scheme | kakenhi | |||||
学位授与機関識別子 | 13601 | |||||
学位授与機関名 | 信州大学(Shinshu university) | |||||
学位の区分 | ||||||
doctoral | ||||||
学位の分野 | ||||||
医学 | ||||||
学位の報告番号 | ||||||
甲第1135号 | ||||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 雑誌に発表。TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE. 244(2):133-144 (2018); doi:10.1620/tjem.244.133. | |||||
資源タイプ(コンテンツの種類) | ||||||
内容記述タイプ | Other | |||||
内容記述 | Thesis | |||||
PubMed | ||||||
識別子タイプ | PMID | |||||
関連識別子 | https://pubmed.ncbi.nlm.nih.gov/29459573/ | |||||
関連名称 | 29459573 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1620/tjem.244.133 | |||||
関連名称 | 10.1620/tjem.244.133 | |||||
権利 | ||||||
権利情報 | © 2018 Tohoku University Medical Press | |||||
出版タイプ | ||||||
出版タイプ | NA | |||||
出版タイプResource | http://purl.org/coar/version/c_be7fb7dd8ff6fe43 | |||||
WoS | ||||||
Web of Science | ||||||
URL | http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000427100700007 |