福克萨1和福克萨2对于肝癌性变态是必不可少的
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
概括
肝细胞癌 (HCC) 呈现性别差异,男性更容易受到影响. 福克萨1/2因子对于性激素对小鼠和人类肝癌发展的影响至关重要.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 分子生物学分子生物学
- 内分泌学 在内分泌学.
背景情况:
- 肝细胞癌 (HCC) 呈现出显著的两性变异,男性的发病率更高.
- 涉及性激素的潜在分子机制在很大程度上是未知的.
研究的目的:
- 研究Foxa1和Foxa2转录因子在性激素依赖的肝细胞癌 (HCC) 调节中的作用.
主要方法:
- 在野生类型和Foxa1/a2缺乏的小鼠中利用了二甲基胺诱导的肝癌发生.
- 分析了Foxa1/a2与雌激素受体 (ERα) 和雄激素受体 (AR) 的目标基因的协调.
- 在人肝样本中的FOXA2结合位点中检查单核酸多态 (SNPs).
主要成果:
- 性二态的HCC在Foxa1/a2缺乏的小鼠中被逆转.
- 在缺陷的小鼠中,Foxa1/a2和ERα/AR对目标基因的同调节丢失了.
- 在FOXA2结合部位的SNP减少了人类肝脏中的FOXA2和ERα结合,并且与女性的HCC相关.
结论:
- 福克萨1/a2因子对于雌激素介导的耐药性和雄激素介导的HCC促进都至关重要.
- 福克萨因子及其点在肝细胞癌的性变异中发挥着中心作用.
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