Poly-(ADP-Ribose) Polymerase-1 Promotes Prothrombin Gene Transcription and Produces Des-Gamma-Carboxy Prothrombin in Hepatocellular Carcinoma
書誌事項
- タイトル
- Poly-(ADP-Ribose) Polymerase-1 Promotes Prothrombin Gene Transcription and Produces Des-Gamma-Carboxy Prothrombin in Hepatocellular Carcinoma
- タイトル別名
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- 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
- 著者
- 谷口, 達哉
- 著者別名
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- タニグチ, タツヤ
- Taniguchi, Tatsuya
- 著者
- 岸, 和弘
- 著者別名
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- キシ, カズヒロ
- Kishi, Kazuhiro
- 著者
- 中川, 忠彦
- 著者別名
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- ナカガワ, タダヒコ
- Nakagawa, Tadahiko
- 著者
- 田中, 宏典
- 著者別名
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- タナカ, ヒロノリ
- Tanaka, Hironori
- 著者
- 田中, 貴大
- 著者別名
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- タナカ, タカヒロ
- Tanaka, Takahiro
- 著者
- 友成, 哲
- 著者別名
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- トモナリ, テツ
- Tomonari, Tetsu
- 著者
- 岡本, 耕一
- 著者別名
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- オカモト, コウイチ
- Okamoto, Koichi
- 著者
- 曽我部, 正弘
- 著者別名
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- ソガベ, マサヒロ
- Sogabe, Masahiro
- 著者
- 宮本, 弘志
- 著者別名
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- ミヤモト, ヒロシ
- Miyamoto, Hiroshi
- 著者
- 岡久, 稔也
- 著者別名
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- オカヒサ, トシヤ
- Okahisa, Toshiya
- 著者
- 六車, 直樹
- 著者別名
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- ムグルマ, ナオキ
- Muguruma, Naoki
- 著者
- カジモト, マユミ
- 著者別名
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- Kajimoto, Mayumi
- 著者
- 佐川, 幾子
- 著者別名
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- サガワ, イクコ
- Sagawa, Ikuko
- 著者
- 高山, 哲治
- 著者別名
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- タカヤマ, テツジ
- Takayama, Tetsuji
- 学位授与大学
- 徳島大学
- 取得学位
- 博士（医学）
- 学位授与番号
- 甲医第1339号
- 学位授与年月日
- 2017-05-25
この論文をさがす
説明
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.