The tissue plasminogen activator gene promoter: a novel tool for radiogenic gene therapy of the prostate?
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.
Marignol
L
L
Department of Haematology and Academic Unit of Clinical and Molecular Oncology, Institute of Molecular Medicine, St James's Hospital and Trinity College Dublin, Ireland.
Robson
T
T
McCarthy
H O
HO
Worthington
J
J
Murray
M M
MM
Hollywood
D
D
Lawler
M
M
Hirst
D G
DG
D000818:Animals; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic / Q000528:radiation effects*; D011467:Prostate / Q000473:pathology / Q000528:radiation effects; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D051381:Rats; D010959:Tissue Plasminogen Activator / Q000235:genetics*; D014162:Transfection; D019076:Transgenes
D049452:Green Fluorescent Proteins; D010959:Tissue Plasminogen Activator