アンドロゲン受容体は,アンドロゲン依存性前立腺がんにおいて,独特の転写プログラムを調節する
Qianben Wang1, Wei Li, Yong Zhang
1Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
Cell
|July 28, 2009
まとめ
アンドロゲン受容体 (AR) は,アンドロゲンがなくても前立腺がんの成長を促します. 進行がんでは,ARは特定の細胞サイクル遺伝子を活性化し,腫瘍の進行と独立した成長を促します.
科学分野:
- 腫瘍学 腫瘍学
- 分子生物学は分子生物学である.
- エピジェネティクス エピジェネティクス
背景:
- 前立腺がんの進行には,アンドロゲン依存状態からアンドロゲン依存状態への移行が含まれます.
- アンドロゲン受容体 (AR) は,両方の段階で重要な役割を果たしますが,先進的で独立した癌におけるその機能は完全に理解されていません.
研究 の 目的:
- 直接AR依存の標的遺伝子を定義し,アンドロゲン依存の前立腺がん細胞におけるARの機能を明らかにする.
- 先進的な前立腺がんにおけるAR媒介遺伝子調節のメカニズムを調査する.
主な方法:
- アンドロゲン依存性および非アンドロゲン依存性がん細胞におけるAR依存性遺伝子発現プロフィールの生成.
- ARシストローム分析により,全ゲノムにわたるAR結合部位をマッピングします.
- 標的遺伝子増強剤における表遺伝子マーク (ヒストンH3K4メチル化) と転写因子結合 (FoxA1) の分析.
主要な成果:
- ARは,アンドロゲン依存性細胞とは異なり,アンドロゲン依存性細胞では,UBE2Cを含むM相細胞サイクル遺伝子を選択的にアップレギュレーションします.
- H3K4メチル化やFoxA1結合などのUBE2C増強剤の表遺伝的変異は,アンドロゲン独立細胞におけるAR結合とUBE2C活性化を促進する.
- ARは,アンドロゲン独立性前立腺がんにおいて,独特の遺伝子発現プログラムを実行し,増殖を促します.
結論:
- アンドロゲン受容体 (AR) は,アンドロゲンに依存しない前立腺がんの成長を促す上で,決定的で明確な役割を果たします.
- 特定のエンハンスターのエピジェネティック調節が,前立腺がんの進行におけるARの機能を決定する.
- この独特なARプログラムをターゲットにすることで,致死性前立腺がんに対する新たな治療戦略が提供されるかもしれません.
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