不同的雌激素受体结合与乳腺癌的临床结果有关
Caryn S Ross-Innes1, Rory Stark, Andrew E Teschendorff
1Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
Nature
|January 6, 2012
概括
雌激素受体α (ER) 在乳腺癌染色质中的结合是动态的. 瘤中获得的ER结合区域与不良的临床结果相关,并预测由FOXA1重编程驱动的复发.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 分子生物学分子生物学
背景情况:
- 雌激素受体α (ER) 是大多数乳腺癌的关键驱动因素.
- 了解ER基因组功能一直仅限于模型系统.
研究的目的:
- 在原发性乳腺癌和转移中映射全基因组ER结合事件.
- 研究ER结合模式与临床结果之间的关系.
- 探索动态ER绑定背后的机制.
主要方法:
- 使用染色体免疫沉,然后使用高通量测序 (ChIP-seq).
- 对原发性乳腺瘤和远程转移进行了分析.
- 对ER和FOXA1结合事件进行了映射,并与临床数据相关联.
主要成果:
- 耐药性癌症保留了ER染色质的招募,但表现出动态结合.
- 初级瘤中独特的ER结合区域与不良的临床结果有关,并预测复发.
- FOXA1调节ER结合的快速重编程,独立于细胞亚群的选择.
- 在转移样本中观察到ER和FOXA1的同时表达.
结论:
- ER结合能力是塑料的,具有与临床结果相关的独特调节元素组合.
- 在乳腺癌中,FOXA1在重新编程ER结合动态方面发挥着至关重要的作用.
- 这项研究在初级瘤中建立了转录因子映射以预测结果.
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