マクロファージ/がん細胞の相互作用は,核受容体脱圧経路によってホルモン抵抗を媒介する
Ping Zhu1, Sung Hee Baek, Eliot M Bourk
1Howard Hughes Medical Institute, Department of Medicine, University of California, San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Cell
|February 14, 2006
まとめ
前立腺がん細胞とマクロファージは,選択的なアンドロゲン受容体アンタゴニスト/調節剤 (SARM) を誘発して遺伝子発現を活性化します. このスイッチには,保存モチーフであるTAB2と炎症信号が含まれ,生殖機能と核受容体の反応を結びつける.
科学分野:
- 分子生物学は分子生物学である.
- エンドクリノロジー エンドクリノロジー
- がん研究 がん研究
背景:
- 転写調節を理解することは,発達,ホメオスタシス,およびホルモン依存性がんの鍵です.
- 選択性アンドロゲン受容体アンタゴニスト/調節剤 (SARM) は,前立腺がんの管理において極めて重要です.
研究 の 目的:
- 抑制から活性化までのSARM機能のスイッチの背後にある分子メカニズムを解明する.
- この機能的なスイッチにおける前立腺がん細胞/マクロファージの相互作用の役割を調査する.
主な方法:
- セックスステロイド受容体における保存されたN端のL/HX7LLモチーフを調査した.
- TAB2のN-CoRコアプレッサー複合体への勧誘を研究した.
- 炎症信号,MEKK1,およびN-CoR/HDAC複合体の解消の役割を調べました.
主要な成果:
- 特定の前立腺がん細胞/マクロファージの相互作用により,SARMの機能が抑制から活性化に切り替わることが発見されました.
- 保存されたL/HX7LLモチーフが特定され,TAB2のN-CoRへの勧誘を媒介する.
- TAB2が炎症信号を感知し,MEKK1をN-CoR/HDACを解除するために採用し,アンドロゲンおよびエストロゲン受容体の標的遺伝子の減圧につながることを実証しました.
結論:
- 保存されたセンサーメカニズムは,炎症と核受容体のリガンド応答を結びつける.
- このメカニズムは,炎症に反応する標的遺伝子の性ステロイド依存抑制を逆転させます.
- この発見は,生殖生物学と癌における核受容体機能と炎症信号伝達経路を結びつけています.
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