Regulation of expression of the Early Growth Response Gene-I (EGR-I) in malignant and benign cells of the prostate

Gloria R. Mora, Kenneth R. Olivier, Richard F. Mitchell, Robert B. Jenkins, Donald J. Tindall

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

BACKGROUND. Expression of the early growth response gene-1 (EGR-1) is elevated in prostate cancer and correlates with tumor progression. This study provides insight into the mechanism(s) that regulate EGR-1 expression and activity in malignant and benign prostate cells. METHODS. Western blotting and in vitro pulse labeling were used to examine EGR-1 protein levels and half-life in malignant (PC-3) and benign (BPH-1) prostate cell lines. EGR-1 functional ability was assessed by transient transfections with an EGR-1 promoter driven luciferase plasmid and electromobility shift assays (EMSAs) to assess DNA binding of the EGR-1 protein. Protein levels of casein kinase II (CKII) were evaluated by Western blotting. RESULTS. PC-3 cells maintain high steady-state levels of EGR-1 protein, in part due to a longer half-life of EGR-1 protein. BPH-1 cells responded to mitogenic stimuli with increased EGR-1 protein levels, and enhanced transcriptional activity. In contrast, PC-3 cells showed no response to stimuli. DNA binding of EGR-1 was higher in BPH-1 cells than in PC-3 cells. This appears to be related to the heavily phosphorylated state of EGR-1 in PC-3 cells which is correlated with increased levels of CKII found in these cells. CONCLUSIONS. PC-3 cells maintain a long lasting, heavily phosphorylated pool of EGR-1, which binds poorly to DNA and responds poorly to mitogenic stimulus. BPH-1 cells, in contrast, maintain a more responsive, less phosphorylated EGR-1 pool. These findings suggest that EGR-1 expression and activity is differentially regulated in PC-3 and BPH-1 cell lines.

Original languageEnglish (US)
Pages (from-to)198-207
Number of pages10
JournalProstate
Volume63
Issue number2
DOIs
StatePublished - May 1 2005

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Keywords

  • BPH-1
  • DNA binding
  • EGR-1
  • PC-3
  • Phosphorylation
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Urology

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