摘要

       雄激素调节基因 (ARG) 库的评估为雄激素受体 (AR) 介导的转录水平信号传导提供了新的见解。定义在正常和恶性前列腺生物学中具有关键功能的 ARG 应该有助于确定前列腺癌 (CaP) 的新生物标志物和治疗靶点。使用 Affymetrix HuGene FL 寡核苷酸阵列，通过层次聚类方法和功能分类分析了广泛使用的激素反应性 LNCaP 细胞中 ARG 的时间表达谱。响应不同雄激素浓度的 ARG 显示出参与特定生化途径的基因的时间共调节。这项研究的重点是我们对参与内质网 (ER) 应激反应途径的基因 (NDRG1、PDIR、HERPUD1、ORP150) 的协调雄激素诱导的新观察。两种选定的内质网应激反应基因 NDRG1 和 HERPUD1 在原发性 CaP 中的表达分析显示肿瘤相关表达显着降低。雄激素信号与 ER 应激反应基因的有趣联系，对蛋白质解折叠或细胞应激信号引起的蛋白质损伤的保护性反应，表明雄激素可能在 CaP 细胞中诱导这种应激信号。两个 ER 应激反应基因的 CaP 相关表达降低也表明该途径在前列腺肿瘤发生中可能被废除。

       The evaluation of the androgen regulatory gene (ARG) library provides new insights into androgen receptor (AR)-mediated transcriptional level signaling. Defining ARG with key functions in normal and malignant prostate biology should help determine new biomarkers and therapeutic targets for prostate cancer (CaP). Using the Affymetrix HuGene FL oligonucleotide array, the time expression profile of ARG in widely used hormone-responsive LNCaP cells was analyzed through hierarchical clustering method and functional classification. ARG in response to different androgen concentrations has shown time co-regulation of genes involved in specific biochemical pathways. The focus of this study is our new observation on the coordinated androgen induction of genes involved in the endoplasmic reticulum (ER) stress response pathway (NDRG1, PDIR, HERPUD1, ORP150). The expression analysis of two selected endoplasmic reticulum stress response genes NDRG1 and HERPUD1 in primary CaP showed that tumor-related expression was significantly reduced. The interesting connection between androgen signaling and ER stress response genes, and the protective response to protein damage caused by protein unfolding or cellular stress signals, suggests that androgens may induce this stress signal in CaP cells. The decreased CaP-related expression of two ER stress response genes also indicates that this pathway may be abolished in prostate tumorigenesis.

https://www.nature.com/articles/1205992