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エストロゲン受容体PAX2によるERBB2の調節は,タモキシフェンに対する反応を決定する
Antoni Hurtado1, Kelly A Holmes, Timothy R Geistlinger
1Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
Nature
|November 14, 2008
まとめ
エストロゲン受容体 (ER) とタモキシフェン複合体は,シス調節要素を介してERBB2転写を直接抑制する. タンパク質PAX2は,この抑制を媒介し,乳がんにおけるタモキシフェン反応に影響を与える.
科学分野:
- 腫瘍学 腫瘍学
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- エストロゲン受容体 (ER) とERBB2/HER-2経路の交差は,乳がんに関与しています.
- これらの経路の間の直接的な転写関連は確立されていない.
研究 の 目的:
- ERとタモキシフェンによるERBB2の直接の転写調節を解明する.
- 乳がん治療への反応に関連するER-ERBB2経路のクロストックにおける主要なメディエーターを特定する.
主な方法:
- 人間の細胞系におけるERBB2転写の分析.
- ペアリングボックス2遺伝子産物 (PAX2) の媒介者としての役割の調査.
- ERBB2の転写制御のためのPAX2とAIB-1/SRC-3の競争の評価.
主要な成果:
- エストロゲン-ERとタモキシフェン-ER複合体は,遺伝子特異的なシス調節要素を通じて,ERBB2の転写を直接抑制する.
- PAX2は,ERとタモキシフェン誘発のERBB2抑制の重要な媒介者として作用する.
- PAX2とERの共同活性化剤であるAIB-1/SRC-3は,ERBB2の調節を競い,タモキシフェン反応を決定する.
結論:
- ER-PAX2相互作用は,ER陽性およびERBB2陽性乳がん亜型間のメカニズム的リンクを提供します.
- この経路は,ER陽性の腫瘍が,ERBB2陽性腫瘍に進行するメカニズムを示唆している.
- 発見は,乳がんにおける内分泌抵抗性についての洞察を提供します.
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