In this study, we have taken advantage of over-expression of eukaryotic translation initiation factor 4E (eIF4E) in prostate cancer cells to design a viral-based targeting system of prostate cancer. Three different lengths of 5 0 -untranslated regions (5 0 UTRs) derived from either fibroblast growth factor-2 (FU-FGF2-GW) or ornithine decarboxylase (FU-ODC 149 -GW and FU-ODC 274 -GW) were inserted upstream of enhanced green fluorescent protein (GFP) gene in a lentiviral backbone. Both nonmalignant control (PNT1B and BPH-1) and neoplastic (LNCaP, C4-2, DU145 and PC-3) prostate cell lines were transfected with each plasmid or virus alone, or in the presence of siRNA against eIF4E, and their expression was monitored via GFP protein levels. Two 5 0 UTRs (FU-FGF2-GW and FU-ODC-GW) were selected as being most sensitive to eIF4E status. Lentiviruses containing these sequences were injected directly into the prostates of PTEN À/À (tumor-bearing) and control mice. Immunofluorescence data and western blot analyses determined that a lentivirus containing a 5 0 UTR derived from FGF-2 is the best candidate for directing selective gene expression in the prostate tumors of PTEN À/À mice in vivo. This study demonstrates that judicious selection of a complex 5 0 UTR can enhance selective targeting of viral-based gene therapies for prostate cancer.
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