ERF突变显示出控制前列腺癌的ETS因子平衡
Rohit Bose1,2, Wouter R Karthaus1, Joshua Armenia1,3
1Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
Nature
|June 15, 2017
概括
前列腺癌
科学领域:
- 分子生物学
- 遗传学
- 癌症学
背景情况:
- 通过上调ERG转录因子, 导致一半的前列腺癌.
- 在前列腺瘤中观察到一种ETS家族成员ERF的反复突变和缺失.
研究的目的:
- 研究ERF突变在前列腺癌中的作用.
- 阐明ERG和ERF在前列腺癌发育和进展中的功能关系.
主要方法:
- 分析ERF突变及其对蛋白质稳定性的影响.
- 在正常小鼠前列腺细胞和前列腺癌细胞系中进行功能研究.
- 染色体免疫沉,然后进行测序 (ChIP-seq),以评估ERF和ERG结合部位.
主要成果:
- ERF突变降低了蛋白质的稳定性,并且与缺乏ERG上调的瘤有关.
- 损失ERF模仿ERG功能增加的表型,包括雄激素受体扩张.
- ERG抑制了ERF的DNA结合,而ERF可以抵消ERG的致癌活性.
结论:
- 它的致癌性涉及瘤抑制剂ERF的竞争和失活.
- 作为一种瘤抑制剂,ERF对抗ERG的致癌功能.
- 这种竞争模式可以扩展到其他致癌转录因子和内源性瘤抑制剂.
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