Foxa1とFoxa2は,肝がんにおける性二形態化に不可欠である
Zhaoyu Li1, Geetu Tuteja, Jonathan Schug
1Department of Genetics and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell
|January 24, 2012
まとめ
肝細胞癌 (HCC) は性別の違いを示しており,男性の方が罹患率が高い. Foxa1/2因子は,性ホルモンがマウスとヒトの肝がん発症に及ぼす影響において極めて重要です.
科学分野:
- 肝臓病理学 肝臓病理学
- 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
背景:
- 肝細胞癌 (HCC) は有意な性二変異を示し,男性では発生率が高くなります.
- 性ホルモンが関与する根本的な分子機構は,ほとんど不明のままである.
研究 の 目的:
- Foxa1およびFoxa2転写因子の性ホルモン依存による肝細胞癌 (HCC) の調節における役割を調査する.
主な方法:
- ワイルドタイプおよびFoxa1/a2欠乏性マウスにおいて,ダイエチルニトロサミン誘発の肝がん発生を活用した.
- Foxa1/a2による標的遺伝子の同調をエストロゲン受容体 (ERα) とアンドロゲン受容体 (AR) で分析した.
- ヒトの肝臓サンプルにおけるFOXA2結合部位における単一ヌクレオチドポリモルフィズム (SNPs) を調べました.
主要な成果:
- 性的二形性HCCは,Foxa1/a2欠乏症のマウスで逆転した.
- Foxa1/a2とERα/ARによる標的遺伝子の同調は,欠乏したマウスでは失われました.
- FOXA2結合部位におけるSNPは,ヒトの肝臓におけるFOXA2およびERα結合を減少させ,女性におけるHCCと相関する.
結論:
- Foxa1/a2因子は,エストロゲン媒介による耐性およびアンドロゲン媒介によるHCCの促進の両方に不可欠です.
- フォクサ因子とその標的は,肝細胞癌の性二形態化に中心的な役割を果たします.
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