前列腺癌是男性生殖系统最常见的恶性肿瘤之一，内分泌治疗后前列腺癌发生激素非依赖转化的分子机制不清，与雄激素受体(AR)及AR共活化/抑制子密切相关。我们在以往的研究中发现核小体结合蛋白1 (NSBP1) 在前列腺癌中过量表达，在激素非依赖性前列腺癌中表达更高，并发挥更重要作用。在近期的研究中，我们进一步发现NSBP1调控组蛋白的磷酸化及AR共活化/抑制子的表达。我们假设 NSBP1 竞争结合组蛋白，使组蛋白修饰表观遗传调控去抑制，AR共活化子表达增加，从而使AR信号通路作用增强，形成去势抵抗性前列腺癌(CRPC)。本课题拟：①研究NSBP1是否介导前列腺癌激素非依赖性转化，探索NSBP1表观调控AR通路基因表达在前列腺癌激素非依赖转化中的分子机制。②建立NSBP1转基因动物模型，研究NSBP1在CRPC形成中的促进作用。③采用临床样本，研究NSBP1表达水平与CRPC表型的关系。

Prostate cancer (PCa) is one of the most common cancer in male reproductive system. The molecular mechanism of castration resistant prostate cancer(CRPC) is not clear, it was reported that this transition is associated with androgen receptor(AR) and AR co-activators/suppressors. In our previous study, we found that nucleosome binding protein 1(NSBP1) was highly expressed in PCa tissue, more highly in CRPC and NSBP1 regulated the phosphorylation of histone and the expression of AR co-activators/suppressors. We assume that NSBP1 binds with histone competitively, disinhibits its modification in the epigenetic regulation pattern and then up-regulates AR co-activators, enhances the AR signaling pathway and promotes the transformation of CRPC. We aim ① to study if NSBP1 mediates the transformation of CRPC and explore the molecular mechanism involved in the epigenetic regulation of AR signaling pathway. ② to setup NSBP1 transgenic animal model and reveal how NSBP1 promotes the transformation of CRPC. ③ to use clinical samples to investigate the relationship between NSBP1 expression and CRPC phenotype.