Regulation of expression of the early growth response gene-1 (EGR-1) in malignant and benign cells of the prostate

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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.