腫瘍細胞は,細胞サイクルヒストン遺伝子プロモーター因子HiNF-Dの緩和を示す
J Holthuis1, T A Owen, A J van Wijnen
1Department of Cell Biology, University of Massachusetts Medical School, Worcester 01655.
Science (New York, N.Y.)
|March 23, 1990
まとめ
ヒストン遺伝子転写の細胞周期調節は,正常な細胞成長に不可欠です. 癌細胞における異常なHiNF-D結合活動は,制御不能な増殖と成長調節の喪失に寄与する.
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
- がん研究 がん研究
背景:
- 細胞周期調節された遺伝子発現は,正常な細胞の成長と発達に不可欠です.
- 厳格な細胞成長制御の喪失は,変形した,腫瘍的現象型の特徴です.
- Sフェーズ中のヒストンタンパク質合成は,DNA複製とクロマチンの包装に不可欠です.
研究 の 目的:
- HiNF-D結合活性の細胞周期調節ヒストン遺伝子転写における役割を調査する.
- 変形細胞と正常細胞におけるHiNF-Dの活性を比較する.
- 変化したHiNF-D活動と腫瘍変異の間の潜在的な関連を解明する.
主な方法:
- 細胞から抽出した核タンパク質を,細胞周期の異なる段階で分析する.
- H4ヒストン遺伝子プロモーターに対するHiNF-D結合活性の測定.
- 正常な二倍体細胞におけるHiNF-D活性と,腫瘍由来または変形細胞系との比較.
主要な成果:
- 正常な細胞は,細胞周期に依存するHiNF-D結合活性を示し,S相でピークに達する.
- トランスフォーメーションされた細胞は,細胞サイクル全体で HiNF-D結合活性が構成的に上昇しています.
- 変異細胞におけるHiNF-Dの活動は,分化時にのみ減少する.
結論:
- H4ヒストン遺伝子プロモーターに変化した構成的なHiNF-D結合は,がんにおける細胞成長調節の喪失と相関する.
- HiNF-Dのこの失調は,腫瘍変異に貢献する重要なメカニズムである可能性があります.
- HiNF-Dの活性をターゲットにすることで,がん治療の治療戦略を提供することができる.
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