腫瘍抑制剤候補の遺伝子スクリーンは,RESTを特定する
Thomas F Westbrook1, Eric S Martin, Michael R Schlabach
1Howard Hughes Medical Institute, Department of Genetics, Harvard Partners Center for Genetics and Genomics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
Cell
|June 18, 2005
まとめ
研究者らは,REST/NRSFを新しい腫瘍抑制遺伝子として特定した. RESTの喪失は,PI(3) Kのシグナル伝達を増やすことで癌を促進し,がん遺伝子発見のための新しい道を開く.
科学分野:
- がん生物学 がん生物学
- 分子腫瘍学 分子腫瘍学
- 遺伝学 遺伝学とは
背景:
- 腫瘍発生には複雑な遺伝的および表遺伝的変化が伴う.
- 悪性変異を誘発する重要な遺伝子を特定することは,がん研究にとって極めて重要です.
研究 の 目的:
- RNAiスクリーンを用いてヒト乳腺上皮細胞の悪性変異を抑制する遺伝子を特定する.
- ガン発症におけるREST/NRSFの役割を調査する.
主な方法:
- 変換抑制剤のためのRNA干渉 (RNAi) ベースの遺伝子スクリーン.
- 遺伝子変異のための配列比較ゲノムハイブリデーション (Array-CGH).
- 結腸直腸がん細胞における変異分析.
主要な成果:
- 既知の腫瘍抑制剤 (TGFBR2,PTEN) と新しい抑制剤であるREST/NRSF.を特定した.
- 結腸直腸がんにおけるRESTの削除と,REST変異の変異を発見した.
- 証明されたREST欠乏細胞は,変換のためのPI ((3) Kシグナリングに依存しています.
結論:
- RESTはヒトの腫瘍抑制剤として機能し,以前は認識されていなかった.
- RESTの喪失は,PI(3) K経路の活性化を通じて癌に寄与する.
- この研究は,新しいがん抑制遺伝子を発見するための方法を提供します.
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