Androgen-induced expression of endoplasmic reticulum (ER) stress response genes in prostate cancer cells

Takehiko Segawa, Martin E. Nau, Linda L. Xu, Rao N. Chilukuri, Mazen Makarem, Wei Zhang, Gyorgy Petrovics, Isabell A. Sesterhenn, David G. McLeod, Judd W. Moul, Maryanne Vahey, Shiv Srivastava*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

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.

Original languageEnglish
Pages (from-to)8749-8758
Number of pages10
JournalOncogene
Volume21
Issue number57
DOIs
StatePublished - 12 Dec 2002
Externally publishedYes

Keywords

  • Androgen regulated genes
  • Endoplasmic reticulum stress response
  • Gene chip
  • Prostate cancer

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