プロゲステロン受容体は,乳がんにおけるERα作用を調節する

Hisham Mohammed¹, I Alasdair Russell¹, Rory Stark¹

¹Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK.

Nature

|July 9, 2015

まとめ

プロゲステロン受容体 (PR) は,乳がんにおけるエストロゲン受容体-α (ERα) の活性を調節する. PR コントロール ERα

科学分野:

エンドクリノロジーエンドクリノロジー
分子生物学は分子生物学である.
腫瘍学腫瘍学

背景:

プロゲステロン受容体 (PR) 発現は,エストロゲン受容体-α (ERα) 機能と乳がんの予後に関する重要なバイオマーカーです.
PRは通常,ERα誘発遺伝子と考えられ,ERαの活性を反映しています.

研究の目的:

ERα標的遺伝子を超えてPRの機能的役割を調査する.
乳がん細胞におけるPRとERαの相互作用を解明する.

主な方法:

クロマチンの免疫プレシピテーション測定法で,ERαとPRの結合を評価する.
転写変化を分析するための遺伝子発現プロファイリング.
生体内異種移植および生体外原発性腫瘍エクスプラント研究.

主要な成果:

PRは,アゴニストリガンドの存在で,ERαと直接結合する.
この結合は,ERα染色体結合を誘導し,独特の遺伝子発現プログラムを確立します.
プロゲステロン治療は,エストロゲン誘発の腫瘍増殖を抑制し,ERαアンタゴニストと併用すると効果が強化された.
PGR遺伝子複製数の喪失は,ERα (((+)) 乳がんのサブセットで観察されました.

結論:

PRは分子リオスタットとして作用し,ERα染色体結合と転写活動を調節する.
これらの発見は,乳がんの予後を理解し,治療戦略を開発するために重要な意味を持っています.

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