Poly-(ADP-Ribose) Polymerase-1 Promotes Prothrombin Gene Transcription and Produces Des-Gamma-Carboxy Prothrombin in Hepatocellular Carcinoma

• 資料種別: 博士論文
• ISSN: 0012-2823
• タイトル: Poly-(ADP-Ribose) Polymerase-1 Promotes Prothrombin Gene Transcription and Produces Des-Gamma-Carboxy Prothrombin in Hepatocellular Carcinoma
• 巻次・部編番号: 95 3
• 著者・編者: Taniguchi, Tatsuya; Kishi, Kazuhiro; Nakagawa, Tadahiko; Tanaka, Hironori; Tanaka, Takahiro; Tomonari, Tetsu; Okamoto, Koichi; Sogabe, Masahiro; Miyamoto, Hiroshi; Okahisa, Toshiya; Muguruma, Naoki; Kajimoto, Mayumi; Sagawa, Ikuko; Takayama, Tetsuji
• 著者標目: Taniguchi, Tatsuya; Kishi, Kazuhiro; Nakagawa, Tadahiko; Tanaka, Hironori; Tanaka, Takahiro; Tomonari, Tetsu; Okamoto, Koichi; Sogabe, Masahiro; Miyamoto, Hiroshi; Okahisa, Toshiya; Muguruma, Naoki; Kajimoto, Mayumi; Sagawa, Ikuko; Takayama, Tetsuji
• 出版事項: Karger AG
• 出版年月日等: 2017-04-07
• 出版年（W3CDTF）: 2017-04-07
• 並列タイトル等: 肝細胞癌におけるDes-gamma-carboxy prothrombinの産生はpoly-(ADP-ribose) polymerase-1によりプロトロンビン遺伝子の転写が亢進することによっておこる; DCP Production Mechanism in HCC
• タイトル（掲載誌）: Digestion
• 授与機関名: 徳島大学
• 授与年月日: 2017-05-25
• 授与年月日（W3CDTF）: 2017-05-25
• 報告番号: 甲第3095号
• 学位: 博士（医学）
• 博論授与番号: 甲第3095号
• 本文の言語コード: eng
• 件名標目: des-gamma-carboxy prothrombin; PARP-1; hepatocellular carcinoma; tumor marker; Biomarkers; Prothrombin
• 対象利用者: 一般
• 一般注記: Background and Aim: Although des-gamma-carboxy prothrombin (DCP) is a well-known tumor marker for hepatocellular carcinoma (HCC), the mechanism of DCP production is unclear. This study aimed to investigate the mechanism how DCP is produced in HCC cells. Methods: Levels of mRNA and DCP were analyzed by real-time polymerase chain reaction and electro-chemiluminescence immunoassay respectively. Secreted alkaline phosphatase (SEAP) expression vectors including deletion mutants of the prothrombin gene promoter were constructed for reporter gene assay. The transcription factors bound to DNA fragments were analyzed by mass spectrometry. An electrophoretic mobility shift assay (EMSA) was performed using a biotin end-labeled DNA. Results: The prothrombin mRNA levels in all 5 DCP producing cell lines were appreciably high. However, those in 2 DCP non-producing cell lines were below detectable levels. A SEAP vector with -2985 to +27 showed a very high transcription activity in DCP-producing Huh-1 cells. However, transcription abruptly decreased when the vector with -2955 to +27 was transfected, and then remained at the similar levels with larger deletion mutants, indicating the existence of a cis-element at -2985 to -2955 (31-bp). Mass spectrometry analysis identified the protein that bound to the 31-bp DNA as poly-(ADP-ribose) polymerase-1 (PARP-1). Knockdown of the PARP-1 gene by small interfering RNA in Huh-1 cells induced marked inhibition of prothrombin gene transcription. The EMSA clearly showed that PARP-1 specifically binds to the 31-bp DNA fragment in the prothrombin gene promoter. Conclusions: Our data suggest that PARP-1 activates prothrombin gene transcription and that the excessive prothrombin gene transcription induces DCP production in DCP-producing HCC cells.
• DOI: info:doi/10.1159/000470837; https://doi.org/info:doi/10.1159/000470837
• 国立国会図書館永続的識別子: info:ndljp/pid/11115944; https://dl.ndl.go.jp/pid/11115944
• 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）: 2018-07-03T21:49:10+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://repo.lib.tokushima-u.ac.jp/110173
• 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