Abstract

The present study examined the effect of the overexpression of early growth response gene (Egr-1) on transforming growth factor beta-1 (TGF-beta 1) and p14(ARF) levels, in PC-3 and LNCaP prostate carcinoma cell lines. Amplification of EGR-1, TGF-beta 1 and p14(ARF) were observed in the two cell lines treated with different stimuli and resulted in a corresponding mRNA and protein expression. The downregulation of TGF-beta 1 and the attenuation of p14(ARF) expression by siRNA against Egr-1 predominantly suggested that TGF-beta 1 and p14(ARF) may be regulated by the transcription factor EGR-1. A marginal attenuation of cell growth in PC-3 and LNCaP prostate carcinoma cell lines overexpressing p14(ARF) was observed. Cells transfected with Egr-1 wild-type were able to grow and avoid cell cycle arrest and apoptosis in the presence or absence of p14(ARF). In addition, EGR-1 stimulated the expression of TGF beta-1 as well as the accumulation of the p14(ARF) proteins. The results suggested that TGF-beta 1 and p14(ARF) activities in the presence of EGR-1 overexpression can exist independently of the presence of cells carrying a mutant p53 (PC-3 cells) or cells carrying a wild-type p53 (LNCaP cells). Thus, the effect of EGR-1 on the growth of prostate carcinoma cells may occur through multiple mechanisms, but be independent of p53 expression control.