ステロイドホルモン受容体は,その強化機能を媒介する要因に競争する
M E Meyer1, H Gronemeyer, B Turcotte
1Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Strasbourg, France.
Cell
|May 5, 1989
まとめ
エストロゲン受容体 (ER) は,HeLa細胞におけるプロゲステロン受容体 (PR) の活動を抑制する. このホルモン受容体間のクロストークは,遺伝子発現に影響を与える重要な転写因子に対する競争を示唆する.
科学分野:
- 分子内分泌学分子内分泌学
- 遺伝子規制 遺伝子規制
- ホルモン受容体の相互作用
背景:
- プロゲステロン受容体 (PR) とエストロゲン受容体 (ER) は,遺伝子転写を調節する重要な核受容体です.
- 異なる核受容体間のクロストークは,ホルモンに対する細胞の反応に影響を与える可能性があります.
研究 の 目的:
- プロゲステロン受容体 (PR) 媒介遺伝子転写に対するエストロゲン受容体 (ER) の抑制効果を調査する.
- ER,PR,およびグルココルチコイド受容体 (GR) 間の転写干渉のメカニズムと範囲を調査する.
主な方法:
- HeLa細胞をレポーター遺伝子とPRとERの発現ベクトルで感染させる.
- 共同発現の研究は,受容体相互作用と転写活性を評価するためのものです.
- 乳がん細胞系における内生受容体相互作用の分析 (T47D,MCF-7).
主要な成果:
- ERは,投与量およびエストロゲンに依存した方法で,PR刺激によるレポーター遺伝子転写を著しく抑制しました.
- ERのN端のA/B領域とホルモン結合ドメインの両方が抑制に関与していた.
- ERはまた,グルココルチコイド受容体 (GR) の活性を抑制し,PR/GRはERの活性を抑制しました.
- 乳がん細胞における内在的なPRとERの間の転写干渉が観察され,pS2遺伝子発現に影響を与えました.
結論:
- エストロゲン受容体 (ER) は,プロゲステロン受容体 (PR) とグルココルチコイド受容体 (GR) の転写活動に積極的に干渉する.
- 発見は,核受容体が転写因子を制限するために競争し,クロストークと遺伝子発現の調節につながる可能性があることを示唆しています.
- この受容体のクロストークは,特に乳がんにおいて,ホルモン主導のプロセスを理解するための意味を持つ.
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