The tissue plasminogen activator gene promoter: a novel tool for radiogenic gene therapy of the prostate?

L. Marignol, T. Robson, H. O. McCarthy, Jenny Worthington, M. M. Murray, D. Hollywood, M. Lawler, D. G. Hirst

    Research output: Contribution to journalArticle

    4 Citations (Scopus)

    Abstract

    Background Radiation therapy is a treatment modality routinely used in cancer management so it is not unexpected that radiation-inducible promoters have emerged as an attractive tool for controlled gene therapy. The human tissue plasminogen activator gene promoter (t-PA) has been proposed as a candidate for radiogenic gene therapy, but has not been exploited to date. The purpose of this study was to evaluate the potential of this promoter to drive the expression of a reporter gene, the green fluorescent protein (GFP), in response to radiation exposure. Methods To investigate whether the promoter could be used for prostate cancer gene therapy, we initially transfected normal and malignant prostate cells. We then transfected HMEC-1 endothelial cells and ex vivo rat tail artery and monitored GFP levels using Western blotting following the delivery of single doses of ionizing radiation (2, 4, 6 Gy) to test whether the promoter could be used for vascular targeted gene therapy. Results The t-PA promoter induced GFP expression up to 6-fold in all cell types tested in response to radiation doses within the clinical range. Conclusions These results suggest that the t-PA promoter may be incorporated into gene therapy strategies driving therapeutic transgenes in conjunction with radiation therapy. Copyright (C) 2008 John Wiley & Sons, Ltd.
    LanguageEnglish
    Pages1032-1038
    JournalJournal of Gene Medicine
    Volume10
    Issue number9
    DOIs
    Publication statusPublished - Sep 2008

    Fingerprint

    Tissue Plasminogen Activator
    Genetic Therapy
    Prostate
    Green Fluorescent Proteins
    Genes
    Radiotherapy
    Radiation
    Background Radiation
    Neoplasm Genes
    Ionizing Radiation
    Transgenes
    Reporter Genes
    Blood Vessels
    Tail
    Prostatic Neoplasms
    Endothelial Cells
    Arteries
    Western Blotting
    Therapeutics
    Neoplasms

    Cite this

    Marignol, L., Robson, T., McCarthy, H. O., Worthington, J., Murray, M. M., Hollywood, D., ... Hirst, D. G. (2008). The tissue plasminogen activator gene promoter: a novel tool for radiogenic gene therapy of the prostate? Journal of Gene Medicine, 10(9), 1032-1038. https://doi.org/10.1002/jgm.1221
    Marignol, L. ; Robson, T. ; McCarthy, H. O. ; Worthington, Jenny ; Murray, M. M. ; Hollywood, D. ; Lawler, M. ; Hirst, D. G. / The tissue plasminogen activator gene promoter: a novel tool for radiogenic gene therapy of the prostate?. In: Journal of Gene Medicine. 2008 ; Vol. 10, No. 9. pp. 1032-1038.
    @article{e6f42627edc648068aa1146f50563bca,
    title = "The tissue plasminogen activator gene promoter: a novel tool for radiogenic gene therapy of the prostate?",
    abstract = "Background Radiation therapy is a treatment modality routinely used in cancer management so it is not unexpected that radiation-inducible promoters have emerged as an attractive tool for controlled gene therapy. The human tissue plasminogen activator gene promoter (t-PA) has been proposed as a candidate for radiogenic gene therapy, but has not been exploited to date. The purpose of this study was to evaluate the potential of this promoter to drive the expression of a reporter gene, the green fluorescent protein (GFP), in response to radiation exposure. Methods To investigate whether the promoter could be used for prostate cancer gene therapy, we initially transfected normal and malignant prostate cells. We then transfected HMEC-1 endothelial cells and ex vivo rat tail artery and monitored GFP levels using Western blotting following the delivery of single doses of ionizing radiation (2, 4, 6 Gy) to test whether the promoter could be used for vascular targeted gene therapy. Results The t-PA promoter induced GFP expression up to 6-fold in all cell types tested in response to radiation doses within the clinical range. Conclusions These results suggest that the t-PA promoter may be incorporated into gene therapy strategies driving therapeutic transgenes in conjunction with radiation therapy. Copyright (C) 2008 John Wiley & Sons, Ltd.",
    author = "L. Marignol and T. Robson and McCarthy, {H. O.} and Jenny Worthington and Murray, {M. M.} and D. Hollywood and M. Lawler and Hirst, {D. G.}",
    year = "2008",
    month = "9",
    doi = "10.1002/jgm.1221",
    language = "English",
    volume = "10",
    pages = "1032--1038",
    journal = "Journal of Gene Medicine",
    issn = "1099-498X",
    number = "9",

    }

    Marignol, L, Robson, T, McCarthy, HO, Worthington, J, Murray, MM, Hollywood, D, Lawler, M & Hirst, DG 2008, 'The tissue plasminogen activator gene promoter: a novel tool for radiogenic gene therapy of the prostate?', Journal of Gene Medicine, vol. 10, no. 9, pp. 1032-1038. https://doi.org/10.1002/jgm.1221

    The tissue plasminogen activator gene promoter: a novel tool for radiogenic gene therapy of the prostate? / Marignol, L.; Robson, T.; McCarthy, H. O.; Worthington, Jenny; Murray, M. M.; Hollywood, D.; Lawler, M.; Hirst, D. G.

    In: Journal of Gene Medicine, Vol. 10, No. 9, 09.2008, p. 1032-1038.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - The tissue plasminogen activator gene promoter: a novel tool for radiogenic gene therapy of the prostate?

    AU - Marignol, L.

    AU - Robson, T.

    AU - McCarthy, H. O.

    AU - Worthington, Jenny

    AU - Murray, M. M.

    AU - Hollywood, D.

    AU - Lawler, M.

    AU - Hirst, D. G.

    PY - 2008/9

    Y1 - 2008/9

    N2 - Background Radiation therapy is a treatment modality routinely used in cancer management so it is not unexpected that radiation-inducible promoters have emerged as an attractive tool for controlled gene therapy. The human tissue plasminogen activator gene promoter (t-PA) has been proposed as a candidate for radiogenic gene therapy, but has not been exploited to date. The purpose of this study was to evaluate the potential of this promoter to drive the expression of a reporter gene, the green fluorescent protein (GFP), in response to radiation exposure. Methods To investigate whether the promoter could be used for prostate cancer gene therapy, we initially transfected normal and malignant prostate cells. We then transfected HMEC-1 endothelial cells and ex vivo rat tail artery and monitored GFP levels using Western blotting following the delivery of single doses of ionizing radiation (2, 4, 6 Gy) to test whether the promoter could be used for vascular targeted gene therapy. Results The t-PA promoter induced GFP expression up to 6-fold in all cell types tested in response to radiation doses within the clinical range. Conclusions These results suggest that the t-PA promoter may be incorporated into gene therapy strategies driving therapeutic transgenes in conjunction with radiation therapy. Copyright (C) 2008 John Wiley & Sons, Ltd.

    AB - Background Radiation therapy is a treatment modality routinely used in cancer management so it is not unexpected that radiation-inducible promoters have emerged as an attractive tool for controlled gene therapy. The human tissue plasminogen activator gene promoter (t-PA) has been proposed as a candidate for radiogenic gene therapy, but has not been exploited to date. The purpose of this study was to evaluate the potential of this promoter to drive the expression of a reporter gene, the green fluorescent protein (GFP), in response to radiation exposure. Methods To investigate whether the promoter could be used for prostate cancer gene therapy, we initially transfected normal and malignant prostate cells. We then transfected HMEC-1 endothelial cells and ex vivo rat tail artery and monitored GFP levels using Western blotting following the delivery of single doses of ionizing radiation (2, 4, 6 Gy) to test whether the promoter could be used for vascular targeted gene therapy. Results The t-PA promoter induced GFP expression up to 6-fold in all cell types tested in response to radiation doses within the clinical range. Conclusions These results suggest that the t-PA promoter may be incorporated into gene therapy strategies driving therapeutic transgenes in conjunction with radiation therapy. Copyright (C) 2008 John Wiley & Sons, Ltd.

    U2 - 10.1002/jgm.1221

    DO - 10.1002/jgm.1221

    M3 - Article

    VL - 10

    SP - 1032

    EP - 1038

    JO - Journal of Gene Medicine

    T2 - Journal of Gene Medicine

    JF - Journal of Gene Medicine

    SN - 1099-498X

    IS - 9

    ER -

    Marignol L, Robson T, McCarthy HO, Worthington J, Murray MM, Hollywood D et al. The tissue plasminogen activator gene promoter: a novel tool for radiogenic gene therapy of the prostate? Journal of Gene Medicine. 2008 Sep;10(9):1032-1038. https://doi.org/10.1002/jgm.1221