title: Androgen-induced expression of endoplasmic reticulum (ER) stress response genes in prostate cancer cells.
abstract: 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.
authors.affiliation: Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Rockville, Maryland, MD 20852, USA.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Segawa
authors.forename: Martin E
authors.initials: ME
authors.lastname: Nau
authors.forename: Linda L
authors.initials: LL
authors.lastname: Xu
authors.forename: Rao N
authors.initials: RN
authors.lastname: Chilukuri
authors.forename: Mazen
authors.initials: M
authors.lastname: Makarem
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Petrovics
authors.forename: Isabell A
authors.initials: IA
authors.lastname: Sesterhenn
authors.forename: David G
authors.initials: DG
authors.lastname: McLeod
authors.forename: Judd W
authors.initials: JW
authors.lastname: Moul
authors.forename: Maryanne
authors.initials: M
authors.lastname: Vahey
authors.forename: Shiv
authors.initials: S
authors.lastname: Srivastava
mesh_terms: D000728:Androgens / Q000378:metabolism / Q000494:pharmacology*; D001483:Base Sequence; D017931:DNA Primers; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D018384:Oxidative Stress / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D000728:Androgens; D017931:DNA Primers