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Nat Commun:前列腺癌细胞AR异质性与不同的雄激素阻断和恩杂鲁胺响应研究

2018-09-06 AlexYang MedSci原创

雄激素受体(AR)在前列腺癌(PCa)中的表达是多样化的,但是AR异质性的功能意义仍旧不清楚。最近,有研究人员筛选了大约200个来源于89名患者的去势抵抗性PCa(CRPC)病灶和全组织包埋切片阐释了AR表达的3中模式:细胞核(nuc-AR)、细胞核/细胞质混合(nuc/cyto-AR)和低/无表达(AR-/lo)。异种种植模型阐释了AR+CRPC对恩杂鲁胺是敏感的,但是AR-/lo CRPC对恩

雄激素受体(AR)在前列腺癌(PCa)中的表达是多样化的,但是AR异质性的功能意义仍旧不清楚。

最近,有研究人员筛选了大约200个来源于89名患者的去势抵抗性PCa(CRPC)病灶和全组织包埋切片阐释了AR表达的3中模式:细胞核(nuc-AR)、细胞核/细胞质混合(nuc/cyto-AR)和低/无表达(AR-/lo)。异种种植模型阐释了AR+CRPC对恩杂鲁胺是敏感的,但是AR-/lo CRPC对恩杂鲁胺是有抵抗性的。基因组编辑获得的AR+和AR-敲除LNCaP细胞克隆展现了不同的生物和致瘤特性以及对恩杂鲁胺不同的的响应。RNA-Seq和生化分析以及实验组合疗法鉴定了BCL-2是关键的治疗靶标,并且为AR+/hi和AR-/lo CRPC提供了概念验证的治疗方案。

最后,研究人员指出,他们的研究将AR表达的异质性与不同的雄激素阻断/恩杂鲁胺响应联系,并且对理解前列腺肿瘤对AR靶标治疗响应的分子基础和促进以AR-/lo为靶标的PCa细胞/克隆的新疗法的发展均具有重要的意义。

原始出处:

Qiuhui Li, Qu Deng, Hsueh-Ping Chao et al. Linking prostate cancer cell AR heterogeneity to distinct castration and enzalutamide responses. Nat Commun. 06 Sep 2018.

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    2018-09-18 liye789132251
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    2019-07-02 liuli5079
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    2018-09-23 13718711b3m

    学习了,值得借鉴与推荐的临床经验,受益匪浅,谢谢分享!

    0

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    2018-09-08 yxch36
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