胃癌細胞株におけるp53発現と抗癌剤(5FU+CDDP)及びサイトカイン(TNFα+IFNγ)によるアポトーシス誘導の特徴-マイクロアレイでの検討-
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概要
- 論文の詳細を見る
胃癌細胞株を用いて,p53発現の有無と抗癌剤及びサイトカインにより誘導されるアポトーシスの特徴をcDNAマイクロアレイを用いた遺伝子発現の変化から検討した。ヒト胃癌細胞株MKN45(p53wild)とMKN28(p53mutant)を用い,low doseの5FU+CDDP或いはTNFα+IFNγと接触させて誘導される遺伝子発現をマイクロアレイを用いて解析し,un-resulate及びdown-regulateした遺伝子を同定した。さらに,uo-regulate及びdown-regulateした数種類の遺伝子に対しRT-PCRを施行し,発現の有無をmRNAレベルで確認した。抗癌剤で誘導されるアポトーシスにおいて,MKN45,MKN28で共通にup-regulateしたものとしてjunBなどがあり,共通にdown-regulateしたのはFADDであった。アポトーシスが高頻度に誘導されたMKN45にのみ特徴的にup-regulateしだのはcaspase3,prefoldinであった.また,caspase8の発現変化は認めなかった。一方,サイトカインによるアポトーシスで特徴的であったのは,抗癌剤によるアポトーシスでは共通にdown-regulateしていたFADDに変化がなく,IGFBP2がdown-regulateしていることであった。low doseの5FU+CDDPで誘導されるアポトーシスでは,転写因子prefoldinが何らかの役割を果たしている可能性が示唆され,サイトカインにより誘導されるアポトーシスではIGFBP2の低発現が重要であると思われた。また,複雑なネットワークをもつアポトーシス経路を解明する上で,多数の遺伝子の変化を一度に解析しうるcDNAマイクロアレイは,有用なツールであり,多彩な新知見が得られる可能性が示唆された。
- 岐阜大学の論文
- 2003-03-31
著者
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佐治 重衡
鷲見病院外科
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TAKAHASHI Takao
Department of Surgical Oncology, Gifu University
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Saji S
Department Of Tumor And General Surgery Division Of Cellular And Molecular Biology Gifu University S
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Saji Shigetoyo
岐阜大学 第1内科
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MATSUI KOJI
Department of Tumor and General Surgery, Gifu University School of Medicine
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KATO HIROKI
Department of Tumor and General Surgery, Gifu University School of Medicine
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SAJI SHIGETOYO
Department of Tumor and General Surgery, Gifu University School of Medicine
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FUKUI TAKAMI
Department of Tumor and General Surgery, Gifu University School of Medicine
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TAKAHASHI Takao
Second Department of Surgery, Gifu University School of Medicine
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Saji Shigetoyo
Department Of Surgery Gifu University School Of Medicine
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Saji Shigehira
Department Of Surgery Tokyo Metropolitan Komagome Hospital
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Saji Shigehira
Division Of Clinical Trials And Research Department Of Breast Surgery And Oncology Tokyo Metropolita
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Saji Shigehira
Department Of Surgery And Breast Oncology Tokyo Metropolitan Komagome Hospital
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Takahashi Takao
Department Of Tumor And General Surgery Division Of Cellular And Molecular Biology Gifu University S
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Kato Hiroki
Department Of Tumor And General Surgery Division Of Cellular And Molecular Biology Gifu University S
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Fukui Takami
Department Of Tumor And General Surgery Division Of Cellular And Molecular Biology Gifu University S
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Fukui Takami
Department Of Oncologic Surgery Gifu University School Of Medicine
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Matsui Koji
Department Of Tumor And General Surgery Division Of Cellular And Molecular Biology Gifu University S
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Takahashi Takao
Department Of Breast Oncology Saitama International Medical Center Saitama Medical University
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Saji Shigehira
Department Of Clinical Trials And Research Tokyo Metropolitan Komagome Hospital
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Kato Hiroki
Department Of Crystalline Materials Science School Of Engineering Nagoya University
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Kato Hiroki
Department Of Cardiovascular Surgery Hokkaido University Hospital
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KATO Hiroki
Department of Applied Chemistry, Faculty of Science, Science University of Tokyo
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