Purine-rich element binding protein (PUR) α induces endoplasmic reticulum stress response, and cell differentiation pathways in prostate cancer cells

Takahiro Inoue, Atsushi Maeno, Conover Talbot, Yu Zeng, David B. Yeater, Eddy S. Leman, Prakash Kulkarni, Osamu Ogawa, Robert H. Getzenberg

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Following androgen ablation treatment for advanced prostate cancer, almost all men relapse after a period of initial response to therapy, which eventually is life threatening. We have previously found that purine-rich element binding protein, PURα, was significantly repressed in androgen-independent prostate cancer cell lines in comparison to an androgen-dependent line. Moreover, over-expressing PURα in androgen-independent prostate cancer cells attenuated their cell proliferation. The aim of the studies described here was to uncover some of the mechanisms by which over-expression of PURα attenuates cell proliferation. METHODS. A set of common genes induced by over-expressing PURα both in PC3 and LNCaP cells was analyzed by DNA microarray. The results were then validated utilizing quantitative reverse transcription-PCR. Using a 5.3-kb region of the PSA promoter containing androgen response elements, the participation of PURα in androgen regulated gene expression was determined. RESULTS. Genes involved in stress response and cell differentiation were induced in cells over-expressing PURα. Some of the genes that are targets of androgen regulation are also induced. Most strikingly, ectopic expression of PURα induced transcriptional activity of the 5.3-kb PSA promoter containing androgen response elements, without androgen stimulation. CONCLUSION. Based upon the consideration that some of the genes involved in cell stress and differentiation are also regulated by androgens our data suggest that PURα shares some common pathways regulated by the androgen receptor. These findings suggest that regulation of PURα expression in prostate cancer cells may serve as a therapeutic target for hormone refractory prostate cancer.

Original languageEnglish (US)
Pages (from-to)861-873
Number of pages13
JournalProstate
Volume69
Issue number8
DOIs
StatePublished - Jun 1 2009

Keywords

  • Differentiation
  • ER stress
  • Prostate cancer
  • Purine-rich element binding protein α

ASJC Scopus subject areas

  • Oncology
  • Urology

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    Inoue, T., Maeno, A., Talbot, C., Zeng, Y., Yeater, D. B., Leman, E. S., Kulkarni, P., Ogawa, O., & Getzenberg, R. H. (2009). Purine-rich element binding protein (PUR) α induces endoplasmic reticulum stress response, and cell differentiation pathways in prostate cancer cells. Prostate, 69(8), 861-873. https://doi.org/10.1002/pros.20936