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

D. A. Boothman, I. W. Lee, W. M. Sahijdak

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39 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalRadiation Research
Volume138
Issue number1 SUPPL.
StatePublished - 1994

Fingerprint

gene therapy
plasminogen activator
Plasminogen Activators
Tissue Plasminogen Activator
Genetic Promoter Regions
Genetic Therapy
isolation
X-radiation
promoter regions
X-Rays
x rays
deoxyribonucleic acid
prokaryotes
ataxia
eukaryotes
anemias
Transcription Factors
protease
Bloom Syndrome
transcription factors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biophysics
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

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title = "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",
abstract = "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.",
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AU - Sahijdak, W. M.

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