異なったエストロゲン受容体結合は,乳がんの臨床結果と関連しています
Caryn S Ross-Innes1, Rory Stark, Andrew E Teschendorff
1Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
Nature
|January 6, 2012
まとめ
乳がんクロマチンのエストロゲン受容体α (ER) 結合はダイナミックである. 腫瘍における獲得されたER結合領域は, FOXA1の再プログラムによって引き起こされる不良の臨床結果と相関し,再発を予測します.
科学分野:
- 腫瘍学 腫瘍学
- ゲノミクスゲノミクスとは
- 分子生物学は分子生物学である.
背景:
- エストロゲン受容体アルファ (ER) は,ほとんどの乳がんの主要な原動力である.
- ERゲノム機能の理解は,モデルシステムに限られていた.
研究 の 目的:
- 原発性乳がんおよび転移における全ゲノムにわたるER結合イベントをマッピングする.
- ER結合パターンと臨床結果との関係を調査する.
- ダイナミックなER結合の背後にあるメカニズムを探求する.
主な方法:
- クロマチンの免疫プレシピテーションとハイスループットシーケンシング (ChIP-seq) を用いた.
- 分析は,原発性乳房腫瘍と遠隔転移を対象に実施した.
- ERおよびFOXA1結合イベントはマッピングされ,臨床データと相関しました.
主要な成果:
- 薬剤耐性がんでは,ERクロマチンのリクルートが維持されるが,ダイナミック・バインディングを示す.
- 主要腫瘍における独特のER結合領域は,不良の臨床結果と関連しており,再発を予測する.
- FOXA1は,細胞亜集団の選択とは無関係に,ER結合の急速な再プログラミングを媒介する.
- ERとFOXA1の共同発現は,転移したサンプルで観察されています.
結論:
- ERの結合能力はプラスチックで,臨床結果と関連した異なる規制要素の組み合わせがあります.
- FOXA1は,乳がんにおけるER結合ダイナミクスを再プログラムする上で重要な役割を果たします.
- この研究では,原発性腫瘍における転写因子マッピングを,結果予測のために確立しています.
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