機能的ゲノミクスによる癌増殖遺伝子発見
Michael R Schlabach1, Ji Luo, Nicole L Solimini
1Howard Hughes Medical Institute and Department of Genetics, Center for Genetics and Genomics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Science (New York, N.Y.)
|February 2, 2008
まとめ
この研究は,癌細胞の成長と生存に不可欠な遺伝子を発見するために,ショートヘアピンRNA (shRNA) を使用した遺伝子スクリーンの新しい方法を導入しています. このプラットフォームは,潜在的ながん薬標的の費用対効果の高い全ゲノム識別を可能にします.
科学分野:
- 遺伝学 遺伝学とは
- 分子生物学は分子生物学である.
- がん研究 がん研究
背景:
- レトロウイルスの短いヘアピンRNA (shRNA) 媒介の遺伝子スクリーンは,哺乳類の細胞における機能喪失のフェノタイプを特定するために不可欠です.
- 細胞の増殖と活性を調節する遺伝子の発見は,がんの生物学を理解し,標的治療の開発に不可欠です.
研究 の 目的:
- 半ヘアピンバーコードを用いたshRNAスクリーニングのための高スループット,マルチプレックスメソドロジーの開発と検証.
- 癌細胞と正常細胞の増殖と生存に不可欠な遺伝子を特定する.
- 異なる細胞系における増殖と生存のために選択的に必要な遺伝子を発見する.
主な方法:
- マイクロアレイ解凍のための半ヘアピンバーコードを備えたマルチプレックスshRNAスクリーニングアプローチを採用しました.
- 細胞増殖と生命力に影響を与えるshRNAを特定するために脱落スクリーンを実施しました.
- 比較分析のために,がんと正常な細胞系の両方に,その方法論を適用した.
主要な成果:
- 細胞の核細胞のプロセス (細胞サイクル,タンパク質翻訳) を標的とした多数のshRNAを特定し,すべての細胞タイプで反増殖的である.
- 特定のがん細胞系における増殖と生存のために選択的に必要とされる遺伝子を発見した.
- 迅速かつ費用対効果の高い全ゲノムスクリーニングのためのプラットフォームの能力を実証しました.
結論:
- 開発されたshRNAスクリーニングプラットフォームは,がんにおける重要な遺伝子を特定するための強力なツールを提供します.
- この方法論は,抗癌薬の開発のための迅速かつ費用対効果の高い標的発見を促進します.
- この発見は,がんゲノムアトラス (The Cancer Genome Atlas) のようなイニシアチブを補完する機能的なゲノム学の視点を提供します.
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