FKBP51调控去势抵抗性前列腺癌形成的分子信号及机制研究

当前临床上缺乏针对去势抵抗性前列腺癌（CRPC）行之有效的治疗手段，归因于其发生发展的机制不明。本项目在课题组前期工作观察到以FK506结合蛋白51（FKBP51）为靶点可抑制CRPC形成的基础上,拟在人前列腺癌新鲜组织构建的NOD-SCID 裸鼠CRPC模型上，观察CRPC形成和进展中FKBP51及其相关分子信号表达的变化，以雄激素受体（AR）激活和失活的两种CRPC细胞为研究对象，分别阐明FKBP51对NF-κB和抗凋亡信号通路的调节机制，探讨AR失活的CRPC中FKBP51受转录因子SOX5调控，激活NF-κB和抗凋亡信号通路，促进CRPC形成和进展的分子机制，以论证FKBP51在AR激活和失活的条件下通过不同的分子信号调节CRPC形成的假说，明确FKBP51在CRPC形成和进展中的分子信号及机制将为CRPC患者的个体化治疗提供新的理论依据和实验基础。

TThere is lack of effective treatment method of castration resistant prostate cancer (CRPC) in current clinical, due to its occurrence and progress mechanism is unknown. The project is Based on our preliminary work that targeting FK506 binding protein 51 (FKBP51) inhibited the CRPC occurrence. We want to observe the change of molecular signal of FKBP51 in CRPC occurrence by prostate cancer tissue SCID CRPC nude mouse model. We regarded androgne receptor(AR) activation and inactivation CRPC cell as research object, observing the mechanism of FKBP51 regulating NF-κB and anti- apoptosis signaling pathways respectively, observing that FKBP51 was regulated by SOX5 and activated the NF-κB and anti-apoptosis signal pathway to promote CPRC occurrence in AR inactivation CRPC, confirming the hypothesis that FKBP51 can regulate CRPC occurrence through the different molecular signal. Under AR activation and inactivation conditions this project discusses FKBP51's molecular signal and mechanism in the occurrence and progress of CRPC,it will provide a new theoretical basis and experimental basis for patients with CRPC individual therapy