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Fibroblast growth factor and ornithine decarboxylase 5′UTRs enable preferential expression in human prostate cancer cells and in prostate tumors of PTEN−/− transgenic mice

Cancer Gene Therapy volume 19, pages 19–29 (2012)Cite this article

Abstract

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′-untranslated regions (5′UTRs) derived from either fibroblast growth factor-2 (FU-FGF2-GW) or ornithine decarboxylase (FU-ODC149-GW and FU-ODC274-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′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−/− (tumor-bearing) and control mice. Immunofluorescence data and western blot analyses determined that a lentivirus containing a 5′UTR derived from FGF-2 is the best candidate for directing selective gene expression in the prostate tumors of PTEN−/− mice in vivo. This study demonstrates that judicious selection of a complex 5′UTR can enhance selective targeting of viral-based gene therapies for prostate cancer.

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Acknowledgements

We thank Dr Latif Wafa for helping in manuscript preparation. We thank Mr Howard Tearle for help in the animal studies. This work was supported by a grant from the Terry Fox Foundation of Canada. MM was supported by a scholarship from the Department of Defense USA, PC073406.

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Authors and Affiliations

  1. Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada

    M Moussavi, N Moshgabadi, L Fazli, E Leblanc, K Zhang & P S Rennie

  2. Department of Medicine, University of British Columbia, Vancouver, BC, Canada

    M Moussavi

  3. Department of Surgery, University of British Columbia, Vancouver, BC, Canada

    W Jia

  4. Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada

    P S Rennie

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  1. M Moussavi
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  2. N Moshgabadi
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  6. W Jia
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  7. P S Rennie
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Correspondence to P S Rennie.

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Moussavi, M., Moshgabadi, N., Fazli, L. et al. Fibroblast growth factor and ornithine decarboxylase 5′UTRs enable preferential expression in human prostate cancer cells and in prostate tumors of PTEN−/− transgenic mice. Cancer Gene Ther 19, 19–29 (2012). https://doi.org/10.1038/cgt.2011.62

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  • DOI: https://doi.org/10.1038/cgt.2011.62

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