ERF変異は,前立腺腫瘍形成を制御するETS因子のバランスを明らかにする
Rohit Bose1,2, Wouter R Karthaus1, Joshua Armenia1,3
1Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
Nature
|June 15, 2017
まとめ
前立腺がん
科学分野:
- 分子生物学
- 遺伝学
- 腫瘍学
背景:
- TMPRSS2-ERGの遺伝子融合は ERGの転写因子を上昇させることで 前立腺がんの半分を誘発します
- ETSファミリーのメンバーであるERFの再発性変異と欠失は前立腺腫瘍で観察されています.
研究 の 目的:
- 前立腺がんにおける ERF 変異の役割を調査する.
- 前立腺がんの発達と進行におけるERGとERFの機能的関係を解明する.
主な方法:
- ERF変異の分析とタンパク質の安定性への影響
- マウスの正常な前立腺細胞と前立腺がん細胞系における機能研究.
- 染色体免疫降水と続いて,ERFとERGの結合部位を評価するシーケンシング (ChIP-seq) を行う.
主要な成果:
- ERF変異はタンパク質の安定性を低下させ,ERGのアップレギュレーションが欠けている腫瘍と関連しています.
- ERFの喪失は,アンドロゲン受容体の拡張を含むERGの機能獲得フェノタイプを模倣する.
- ERGはERFのDNA結合を阻害し,ERFはERGの腫瘍性活性に対抗することができる.
結論:
- ERGの腫瘍性には,腫瘍抑制剤ERFとの競合と無効化が含まれています.
- ERFは腫瘍抑制剤として作用し,ERGの腫瘍性機能に反する.
- この競争モデルは,他の腫瘍性転写因子および内生性腫瘍抑制剤にも適用できる.
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