超酸化物を生成する酸化酵素Mox1による細胞変異
Y A Suh1, R S Arnold, B Lassegue
1Department of Biochemistry, Emory University Medical School, Atlanta, Georgia 30322, USA.
Nature
|September 15, 1999
まとめ
反応性酸素種 (ROS) は,がんと細胞成長に関連しています. 新しく特定された遺伝子であるmox1は,非ファゴサイト細胞でROSを生成し,細胞増殖と腫瘍形成を促します.
科学分野:
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
- 腫瘍学 腫瘍学
背景:
- 反応性酸素種 (ROS) は,ミトゲンシグナル伝達と癌の発生に役割を果たします.
- 多くの癌細胞でROSの増産が観察され,増殖と相関しています.
研究 の 目的:
- 非ファゴサイト細胞におけるROS生成に関与する新しい遺伝子を特定し,特徴づけること.
- 細胞の成長,増殖,腫瘍形成におけるこの遺伝子の役割を調査する.
主な方法:
- gp91phox.の同型であるmox1遺伝子のクローニング.
- 様々な組織におけるmox1 mRNA発現の分析.
- ROS生成と細胞成長に対するmox1操作 (反感覚,過剰表現) の効果を in vitroで調査する.
- 腫瘍形成の評価は,アティミックなマウスを用いて in vivo で行われました.
主要な成果:
- mox1は,超酸化物を生成するNADPH酸化酵素ホモログをコードし,結腸,前立腺,子宮,および血管の滑らかな筋肉で発現します.
- 血小板由来成長因子は,滑らかな筋肉細胞におけるmox1 mRNAを誘導する.
- Antisense mox1は超酸化物生成と成長を減少させ,mox1の過剰発現は超酸化物生成と細胞成長を増加させた.
- mox1を発現する細胞は,変異したフェノタイプ,アンカレージ独立の成長を示し,マウスで腫瘍を形成した.
結論:
- mox1遺伝子は,ROSの産生を非ファゴサイト細胞の成長制御と結びつけている.
- mox1は細胞増殖の重要な調節体であり,腫瘍発生の可能性を示しています.
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