雄激素受体与中介复合物的相互作用在去势抵抗性前列腺癌中通过 CDK7 对 MED1 的磷酸化作用得到增强。
Androgen Receptor Interaction with Mediator Complex Is Enhanced in Castration-Resistant Prostate Cancer by CDK7 Phosphorylation of MED1.
机构信息
Hematology-Oncology Division, Department of Medicine and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
出版信息
Cancer Discov. 2019 Nov;9(11):1490-1492. doi: 10.1158/2159-8290.CD-19-1028.
Abstract
In this issue of , Rasool and colleagues show that TF11H/CDK7 phosphorylates the MED1 component of the Mediator complex, which enhances its interaction with androgen receptor (AR), and that this phosphorylation is increased in prostate cancer that is resistant to castration and enzalutamide. A covalent CDK7-specific inhibitor (THZ1) impairs AR-mediated MED1 recruitment to chromatin, and can suppress enzalutamide resistance and induce tumor regression in a castration-resistant prostate cancer xenograft model, suggesting a novel therapeutic approach for advanced prostate cancer..
摘要
在本期 杂志中，Rasool 及其同事表明，TF11H/CDK7 使中介体复合物的 MED1 组分发生磷酸化，从而增强其与雄激素受体（AR）的相互作用，并且这种磷酸化在对去势和恩杂鲁胺耐药的前列腺癌中增加。一种共价 CDK7 特异性抑制剂（THZ1）损害了 AR 介导的 MED1 向染色质的募集，并且可以抑制恩杂鲁胺耐药 并在去势抵抗性前列腺癌异种移植模型中诱导肿瘤消退，提示晚期前列腺癌的一种新的治疗方法。
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本文引用的文献
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