前列腺癌一旦由雄激素依赖性向非依赖性生长转变，临床预后极差。研究表明，雄激素剥夺治疗过程中肿瘤局部出现的缺氧环境会导致该转变的发生。本项目组前期发现，TXNDC5在前列腺癌中过表达，并可受缺氧和雄激素的双重调控表达上调。为了进一步明确TXNDC5的功能以及在雄激素非依赖性生长转变过程中发挥的作用，我们拟通过检测TXNDC5在不同类型前列腺癌中的表达特点和临床意义；在雄激素剥夺和/或缺氧诱导条件下，采用强制性高表达/沉默TXNDC5的方法，体内外实验证明它对细胞功能的影响，并检测雄激素受体和TXNDC5是否存在相互作用和调控关系；蛋白质组学法寻找与TXNDC5相互作用蛋白等方面，多角度验证TXNDC5在前列腺癌中高表达的意义，进一步揭示癌细胞发生雄激素非依赖性生长转变的分子机制，为临床诊断以及靶向性治疗提供实验线索和理论依据。

In general, primary PCa is an androgen-dependent disease and is highly responsive to androgen ablation therapy. However, PCa eventually will recur and progress to castration-resistant prostate cancer (CRPC) after hormone therapy. CRPC is the lethal form of PCa. Our previous results showed that TXNDC5 expression, which was up-regulated by hypoxia and androgen, overexpressed in Pca tissues. In order to study the function of TXNDC5 in tumorigenesis and whether or not, it was accounted for castration-resistant Pca progression, the following studies are needed. Firstly,we would clarify the characters and clinical significance of TXNDC5 expression in different kinds of Pca. Secondly,under the androgen-deprivation and/or hypoxia conditions,the functions of TXNDC5 on PCa cells would be studied after up/down-regulation of its expression in vitro and vivo. Furhermore, the relationship between TXNDC5 and androgen receptor would be studied as well. Proteomics would also be applied to screen proteins interacting with TXNDC5. All together, we would study the effects of TXNDC5 on cell biological functions from different aspects as well as the molecular mechanism of the progression from androgen-dependence to castration-resistant to make diagnosis and targeting treatment feasible and applicable.