Inhibition of cell death and induction of G2 arrest accumulation in human ovarian clear cells by HNF-1β transcription factor: chemosensitivity is regulated by checkpoint kinase CHK1.

• 資料種別: 博士論文
• ISSN: 1048-891X
• タイトル: Inhibition of cell death and induction of G2 arrest accumulation in human ovarian clear cells by HNF-1β transcription factor: chemosensitivity is regulated by checkpoint kinase CHK1.
• 巻次・部編番号: 24 5
• 著者・編者: Shigetomi, Hiroshi; Sudo, Tamotsu; Shimada, Keiji; Uekuri, Chiharu; Tsuji, Yoriko; Kanayama, Seiji; Naruse, Katsuhiko; Yamada, Yoshihiko; Konishi, Noboru; Kobayashi, Hiroshi
• 著者標目: Shigetomi, Hiroshi; Sudo, Tamotsu; Shimada, Keiji; Uekuri, Chiharu; Tsuji, Yoriko; Kanayama, Seiji; Naruse, Katsuhiko; Yamada, Yoshihiko; Konishi, Noboru; Kobayashi, Hiroshi
• 出版事項: Lippincott Williams & Wilkins
• 出版年月日等: 2014-06; 24 5
• 出版年（W3CDTF）: 2014-06
• 並列タイトル等: 卵巣明細胞腺癌における転写因子HNF-1βはDNA損傷チェックポイント機構の一つであるCHK1タンパクを制御し、抗癌剤耐性を獲得する
• タイトル（掲載誌）: International journal of gynecological cancer
• 授与機関名: 奈良県立医科大学
• 授与年月日: 2014-12-03
• 授与年月日（W3CDTF）: 2014-12-03
• 報告番号: 乙第1345号
• 学位: 博士（医学）
• 博論授与番号: 乙第1345号
• 本文の言語コード: eng
• 件名標目: Transcription factors; DNA damage response; Cell cycle; Checkpoint control; Chemoresistance
• 対象利用者: 一般
• 一般注記: type:Thesis; ObjectiveAppropriate cell cycle checkpoints are essential for the maintenance of normal cells and chemosensitivity of cancer cells. Clear cell adenocarcinoma (CCA) of the ovary is highly resistant to chemotherapy. Hepatocyte nuclear factor-1β (HNF-1β) is known to be overexpressed in CCA, but its role and clinical significance is unclear. We investigated the role of HNF-1β in regulation of the cell cycle in CCA.MethodsTo clarify the effects of HNF-1β on cell cycle checkpoints, we compared the cell cycle distribution and the expression of key proteins involved in CCA cells in which HNF-1β had been stably knocked down and in vector-control cell lines after treatment with bleomycin. HNF-1β (+) cells were arrested in G2 phase because of DNA damage.ResultsHNF-1β (−) cells died because of a checkpoint mechanism. G2 arrest of HNF-1β (+) cells resulted from sustained CHK1 activation, a protein that plays a major role in the checkpoint mechanism. HNF-1β (+) cells were treated with a CHK1 inhibitor after bleomycin treatment. Flow cytometric analysis of the cell cycle demonstrated that DNA damage–induced G2-arrested cells were released from the checkpoint and killed by a CHK1 inhibitor.ConclusionsThe chemoresistance of CCA may be due to aberrant retention of the G2 checkpoint through overexpression of HNF-1β. This is the first study demonstrating cell cycle regulation and chemosensitization by a CHK1 inhibitor in CCA.; 博士（医学）・乙第1345号・平成26年12月3日; © 2014 by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology.; identifier:International journal of gynecological cancer Vol.24 No.5 p.838-843; identifier:1048891X; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2749; identifier:International journal of gynecological cancer, 24(5): 838-843
• DOI: info:doi/10.1097/IGC.0000000000000136; https://doi.org/info:doi/10.1097/IGC.0000000000000136
• 国立国会図書館永続的識別子: info:ndljp/pid/9479058; https://dl.ndl.go.jp/pid/9479058
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• コレクション（個別）: 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2015-08-01T14:40:15+09:00
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: 国立国会図書館内限定公開
• デジタル化資料送信: 図書館・個人送信対象外
• 遠隔複写可否（NDL）: 可
• 掲載誌（URI）: http://hdl.handle.net/10564/2749
• 連携機関・データベース: 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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