Oncogene:GRK2能够增强前列腺和前列腺肿瘤的雄激素受体依赖性

2020-02-01 AlexYang MedSci原创

发展成为雄激素阻断治疗抗性的转移性肿瘤是前列腺癌治疗的主要挑战。尽管这些复发性肿瘤依赖于雄激素受体(AR),非AR驱使的肿瘤也越来越流行且致死。最近,有研究人员呈现了一个新的遗传工程建立的非AR驱使的前列腺癌小鼠模型,并聚焦一个与G蛋白耦合的受体负调控因子,该因子在恶性人类前列腺肿瘤中下调。因此,转基因小鼠模型中,前列腺特异性表达显性-负G蛋白偶联受体激酶2 (GRK2-DN)能够减少AR和AR靶

发展成为雄激素阻断治疗抗性的转移性肿瘤是前列腺癌治疗的主要挑战。尽管这些复发性肿瘤依赖于雄激素受体(AR),非AR驱使的肿瘤也越来越流行且致死。

最近,有研究人员呈现了一个新的遗传工程建立的非AR驱使的前列腺癌小鼠模型,并聚焦一个与G蛋白耦合的受体负调控因子,该因子在恶性人类前列腺肿瘤中下调。因此,转基因小鼠模型中,前列腺特异性表达显性-负G蛋白偶联受体激酶2 (GRK2-DN)能够减少AR和AR靶基因在前列腺中的表达,并对去势产生的退化产生抗性。更多的是,GRK2-DN转基因能够通过增加原发性肿瘤的大小、促进内脏器官转移、抑制AR和诱导神经内分泌标记mRNAs剧烈地加速肿瘤基因起始的前列腺致瘤过程。

最后,研究人员指出,GRK能够增强前列腺的AR依赖性,GRK2功能在前列腺肿瘤中的缺失能够加速疾病朝向致死阶段发展。

原始出处:

Adam J. Adler, Payal Mittal, Adam T. Hagymasi et al. GRK2 enforces androgen receptor dependence in the prostate and prostate tumors. Oncogene. 20 Jan 2020

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    2020-08-08 cy0324
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    2020-02-03 zsyan

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