インターフェロン誘導6-16遺伝子の発現とその機能解析

• 研究課題/領域番号: 08265103
• 研究種目: 特定領域研究(A)
• 配分区分: 補助金
• 研究機関: 広島大学
• 研究代表者: 田原 榮一 (川原 榮一) 広島大学, 医学部, 教授 (00033986)
• 研究分担者: 横崎 宏 広島大学, 医学部, 講師 (10200891) ; 安井 弥 広島大学, 医学部, 助教授 (40191118) ; 松本 邦夫 大阪大学, 医学部, 助教授 (90201780) ; 加藤 洋 癌研究所, 病理部, 部長 (20010473) ; 井藤 久雄 鳥取大学, 医学部, 教授 (60127610) ; 広橋 説雄 国立がんセンター研究所, 副所長 (70129625) ; 佐々木 博己 国立がんセンター研究所, 分子腫瘍学部, 室長 (60235265) ; 磯村 実 癌研, 癌化学療法センターゲノム解析研究部, 研究員 (40272497)
• 研究期間 (年度): 1999
• 研究課題ステータス: 完了 (1999年度)
• 配分額: 118,500千円 (直接経費: 118,500千円); 1999年度: 7,500千円 (直接経費: 7,500千円); 1998年度: 37,000千円 (直接経費: 37,000千円); 1997年度: 37,000千円 (直接経費: 37,000千円); 1996年度: 37,000千円 (直接経費: 37,000千円)
• キーワード: 6-16 gene / apoptosis / CIB / Bcl-2 / caspase-3 / cytochrome c / 5-FU / cycloheximide / ヒト消化器がん / 6-16遺伝子 / c-ERBB2遺伝子 / β-カテニン / Tcr / lef / HGF / アポトーシス / インターフェロン / c-erbB-2 / カドヘリン / カテニン

研究概要

インターフェロン誘導遺伝子6-16は、細胞の老化に伴い発現が増加し、また胃癌、大腸癌の腫瘍細胞で高発現し、その上、様々なストレスによっても発現が増加してくる。一方、6-16は、サイクロヘキシミド、5-FU、無血清条件下において誘導されるアポトーシスを抑制し、その機構は、caspase-3活性に依存し、ミトコンドリアからのチトクロム_cの放出を抑制していることが明らかとなった。即ち、6-16は、ミトコンドリアに局在し、新しいミトコンドリアに関連したアポトーシス抑制蛋白質であることが明らかにされた。また6-16蛋白質は、Yeast Two-Hybrid法からCIB(Calucium-Integrin Binding Protein)と結合する。CIBは、Bcl-2と結合し、アポトーシスを促進する蛋白質である可能性があり、6-16とCIBさらにはBcl-2蛋白質ファミリーのバランスでアポトーシスを調節している可能性が考えられた。現在、6-16とCIBのノックアウトマウス、トランスジェニックマウスの作製により、個体レベルでの解析を行なっている。

研究成果

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