GSK-3β mediates the effects of HNF-1β overexpression in ovarian clear cell carcinoma. 5

• 資料種別: 博士論文
• タイトル: GSK-3β mediates the effects of HNF-1β overexpression in ovarian clear cell carcinoma.
• 巻次・部編番号: 20 5
• 著者・編者: Kawahara, Naoki; Mizutani, Ayano; Matsubara, Sho; Takeda, Yoshinori; Kobayashi, Hiroshi
• 著者標目: Kawahara, Naoki; Mizutani, Ayano; Matsubara, Sho; Takeda, Yoshinori; Kobayashi, Hiroshi
• 出版事項: Spandidos
• 出版年月日等: 2020-11; 20 5
• 出版年（W3CDTF）: 2020-11
• 並列タイトル等: HNF-1β過剰発現を呈する卵巣明細胞癌においてGSK-3βは新たなシグナル伝達経路を介在する
• タイトル（掲載誌）: Experimental and therapeutic medicine
• 掲載ページ: Article No.122-
• ISSN（掲載誌）: 17920981
• 授与機関名: 奈良県立医科大学
• 授与年月日: 2021-03-15
• 授与年月日（W3CDTF）: 2021-03-15
• 報告番号: 甲第785号
• 学位: 博士（医学）
• 博論授与番号: 甲第785号
• 本文の言語コード: eng
• 件名標目: ovarian clear cell carcinoma; glycogen synthase kinase-3β; hepatocyte nuclear factor-1β; nuclear factor-κB
• 対象利用者: 一般
• 一般注記: type:Thesis; Deubiquitinase USP28 is a target gene of the transcription factor HNF1 homeobox β (HNF-1β), which promotes the survival of ovarian clear cell carcinoma (OCCC) cell lines. However, the pharmacological inhibition of HNF-1β can cause several adverse effects as it is abundantly expressed in numerous organ systems, including the kidney, liver, pancreas and digestive tract. Therefore, small interfering RNA (siRNA) screening was performed in the current study to identify other potential downstream targets of the HNF-1β-mediated pathway. The results revealed that glycogen synthase kinase-3β (GSK-3β) may be a potential downstream target affecting cell viability. To further clarify the effects of GSK-3β, two human OCCC cell lines, TOV-21G (HNF-1β overexpressing line) and ES2 (HNF-1β negative) were transfected with siRNA targeting GSK-3β or control vectors. Loss-of-function studies using RNAi-mediated gene silencing indicated that HNF-1β facilitated GSK-3β expression, resulting in the loss of phosphorylated nuclear factor-κB (p-NFκB) and the reduction of TOV-21G cell proliferation. The cell proliferation assay also revealed that GSK-3β inhibitors rescued the effects of HNF-1β silencing on cell viability in a dose-dependent manner. Furthermore, the GSK-3β inhibitor, AR-A014418, effectively inhibited tumor cell proliferation in a xenograft mouse model. In conclusion and to the best of our knowledge, the current study was the first to determine that GSK-3β is a target gene of HNF-1β. In addition, the results of the present study revealed the novel HNF-1β-GSK-3β-p-NFκB pathway, occurring in response to DNA damage. Targeting this pathway may therefore represent a putative, novel, anticancer strategy in patients with OCCC.; 博士（医学）・甲第785号・令和3年3月15日; Copyright: © Kawaharaet al. This is an open access article distributed under theterms of CreativeCommons Attribution License(https://creativecommons.org/licenses/by-nc-nd/4.0/).; identifier:Experimental and therapeutic medicine Vol.20 No.5 Article No.122 (2020 Nov); identifier:17920981; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3909; identifier:Experimental and therapeutic medicine, 20(5): Article No.122
• 国立国会図書館永続的識別子: info:ndljp/pid/12070977; https://dl.ndl.go.jp/pid/12070977
• 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）: 2022-02-06T04:33:19+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
• 関連情報（URI）: https://doi.org/10.3892/etm.2020.9250
• 掲載誌（URI）: http://hdl.handle.net/10564/3909
• 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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