Poly-(ADP-Ribose) Polymerase-1 Promotes Prothrombin Gene Transcription and Produces Des-Gamma-Carboxy Prothrombin in Hepatocellular Carcinoma 95 3

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

Persistent ID (NDL): info:ndljp/pid/11115944

Material type: 博士論文

Author: Taniguchi, Tatsuyaほか

Publisher: Karger AG

Publication date: 2017-04-07

Material Format: Digital

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Name of awarding university/degree: 徳島大学,博士（医学）

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Note (General)：: Background and Aim: Although des-gamma-carboxy prothrombin (DCP) is a well-known tumor marker for hepatocellular carcinoma (HCC), the mechanism of DCP...

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Material Type: 博士論文
ISSN: 0012-2823
Title: Poly-(ADP-Ribose) Polymerase-1 Promotes Prothrombin Gene Transcription and Produces Des-Gamma-Carboxy Prothrombin in Hepatocellular Carcinoma
Volume: 95 3
Author/Editor: 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
Author Heading: 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
Publication, Distribution, etc.: Karger AG
Publication Date: 2017-04-07
Publication Date (W3CDTF): 2017-04-07
Alternative Title: 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
Periodical title: Digestion
Degree grantor/type: 徳島大学
Date Granted: 2017-05-25
Date Granted (W3CDTF): 2017-05-25
Dissertation Number: 甲第3095号
Degree Type: 博士（医学）
Conferring No. (Dissertation): 甲第3095号
Text Language Code: eng
Subject Heading: des-gamma-carboxy prothrombin
PARP-1
hepatocellular carcinoma
tumor marker
Biomarkers
Prothrombin
Target Audience: 一般
Note (General): 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
Persistent ID (NDL): info:ndljp/pid/11115944
https://dl.ndl.go.jp/pid/11115944
Collection: 障害者向け資料
Collection (Materials For Handicapped People:1): テキストデータ
Collection (particular): 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
Acquisition Basis: 博士論文（自動収集）
Date Accepted (W3CDTF): 2018-07-03T21:49:10+09:00
Format (IMT): application/pdf
Access Restrictions: 国立国会図書館内限定公開
Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
Availability of remote photoduplication service: 可
Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/110173
Data Provider (Database): 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