Androgen-induced expression of endoplasmic reticulum (ER) stress response genes in prostate cancer cells
Androgen-induced expression of endoplasmic reticulum (ER) stress response genes in prostate cancer cells
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DOI：
10.1038/sj.onc.1205992
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发表时间：
2002-12-12
期刊：
影响因子：
8
通讯作者：
Srivastava, S
中科院分区：
文献类型：
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作者：
Segawa, T;Nau, ME;Srivastava, S
雄激素调节基因(ARG)谱的评估为在转录水平上了解雄激素受体(AR)介导的信号提供了新的见解。在正常和恶性前列腺癌生物学中具有关键功能的ARGs的定义应有助于确定前列腺癌(CAP)的新生物标志物和治疗靶点。利用Affymetrix Hugene FL寡核苷酸阵列，通过系统聚类法和功能分类，分析了ARGs在广泛应用的激素反应性LNCaP细胞中的时间表达谱。ARGs对不同的雄激素浓度的反应表明，参与特定生化途径的基因在时间上是共同调节的。本研究主要研究内质网(ER)应激反应途径中雄激素协同诱导基因(NDRG1、PDIR、HERPUD1、ORP150)的诱导作用。对两个选定的ER应激反应基因NDRG1和HERPUD1在原发CAP中的表达分析显示，肿瘤相关表达显著降低。有趣的是，雄激素信号与内质网应激反应基因的联系，一种对细胞应激信号引起的蛋白质展开或蛋白质损伤的保护性反应，表明雄激素可能在帽细胞中诱导这种应激信号。两个内质网应激反应基因CAP相关表达的降低也表明这一途径可能在前列腺癌的发生中被取消。
Evaluations of androgen regulated gene (ARG) repertoire provide new insights into the androgen receptor (AR) mediated signaling at the transcriptional level. Definition of ARGs having critical functions in the biology of normal and malignant prostate should aid in identifying new bio-markers and therapeutic targets for prostate cancer (CaP). Using Affymetrix HuGene FL oligonucleotide arrays, temporal expression profiles of ARGs in widely used hormone responsive LNCaP cells, were analysed by hierarchical clustering methods and functional classification. ARGs in response to different androgen concentrations showed temporal co-regulation of genes involved in specific biochemical pathways. This study focuses on our new observations of the coordinated androgen induction of genes (NDRG1, PDIR, HERPUD1, ORP150) involved in the endoplasmic reticulum (ER) stress response pathway. Expression analysis of the two selected ER stress responsive genes, NDRG1 and HERPUD1 in primary CaPs revealed a significantly reduced tumor associated expression. Intriguing linkage of the androgen signaling to ER stress responsive genes, a protective response to protein unfolding or protein damage resulting from cellular stress signals, suggests that androgens may induce such stress signals in CaP cells. Decreased CaP associated expression of two ER stress responsive genes also suggests that possible abrogation of this pathway in prostate tumorigenesis.