Isolation of an X-ray-responsive element in the promoter region of tissue-type plasminogen activator : potential uses of X-ray-responsive elements for gene therapy

• Published in: Radiation research 1994-04, Vol.138 (1), p.S68-S71
• Main Authors: BOOTHMAN, D. A, LEE, I. W, SAHIJDAK, W. M
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cell Nucleus - enzymology; Dose-Response Relationship, Radiation; Genetic Therapy; Humans; Medical sciences; Other treatments; Promoter Regions, Genetic - radiation effects; Tissue Plasminogen Activator - biosynthesis; Tissue Plasminogen Activator - genetics; Tissue Plasminogen Activator - radiation effects; Treatment. General aspects; Tumor Cells, Cultured; Tumors
• ISSN: 0033-7587; 1938-5404
• DOI: 10.2307/3578765

Tissue-type plasminogen activator (t-PA) was induced over 50-fold after X irradiation in radioresistant human melanoma cells (Boothman et al., Cancer Res. 51, 5587-5595, 1991). Activities of t-PA were induced 14-fold in ataxia telangiectasia, 9-fold in Bloom's syndrome and 6-fold in Fanconi's anemia cells, compared to normal human fibroblasts (Fukunaga et al., Int. J. Radiat. Oncol. Biol. Phys. 24, 949-957, 1992). X-ray-inducible synthesis of the protease, t-PA, may play a role(s) in damage-inducible repair processes in mammalian cells, similar to the SOS repair systems in lower eukaryotes and prokaryotes. DNA band shift and DNase I footprinting assays were used to determine binding if transcription factors to a previously unknown X-ray-responsive element (XRE) in the t-PA promoter. The major goals of our research with XREs are to understand (a) which transcription factor(s) regulates t-PA induction after X rays, and (b) the role(s) of t-PA in DNA repair, apoptosis or other responses to X rays. The purpose of this paper is to discuss the potential use of an XRE, such as the one in the t-PA promoter, for gene radiotherapy. Several gene therapy strategies are proposed.