Low-dose radiation response of the p21(WAF1/CIP1) gene promoter transduced by adeno-associated virus vector.
- Author:
Mitsuru NENOI
1
;
Kazuhiro DAINO
;
Sachiko ICHIMURA
;
Shin Ichiro TAKAHASH
;
Teruo AKUTA
Author Information
1. Radiation Effect Mechanisms Research Group, National Institute of Radiological Sciences, 9-1, Anagawa-4-chome, Inage-ku, Chiba 263-8555, Japan. m_nenoi@nirs.go.jp
- Publication Type:Original Article ; Evaluation Studies ; Research Support, Non-U.S. Gov't
- Keywords:
cyclin-dependent kinase inhibitor p21;
dependovirus;
dTMP kinase;
gene therapy;
promoter regions (genetic);
radiation;
simplexvirus
- MeSH:
X-Rays;
Tumor Cells, Cultured;
Transgenes/*radiation effects;
Transduction, Genetic;
Promoter Regions (Genetics)/*radiation effects;
Humans;
Genetic Vectors/*radiation effects;
Gene Therapy/methods;
Electroporation/methods;
Dose-Response Relationship, Radiation;
Cyclin-Dependent Kinase Inhibitor p21/*genetics;
Adenoviridae;
3' Untranslated Regions/physiology
- From:Experimental & Molecular Medicine
2006;38(5):553-564
- CountryRepublic of Korea
- Language:English
-
Abstract:
In cancer gene therapy, restriction of antitumor transgene expression in a radiation field by use of ionizing radiation-inducible promoters is one of the promising approaches for tumor-specific gene delivery. Although tumor suppressor protein p53 is induced by low doses (<1 Gy) of radiation, there have been only a few reports indicating potential utilization of a p53-target gene promoter, such as that of the p21 gene. This is mainly because the transiently transfected promoter of p53-target genes is not much sensitive to radiation. We examined the response of the p21 gene promoter to low-dose radiation when transduced into a human breast cancer cell line MCF-7 by use of recombinant adeno-associated virus (rAAV) vectors. It was shown that the p21 gene promoter transduced by rAAV vectors was more highly radiation-responsive than that transiently transfected by electroporation. A significant induction of the p21 gene promoter by radiation of low doses down to 0.2 Gy was observed. When cells were transduced with the p21 gene promoter-driven HSVtk gene by rAAV vector, they were significantly sensitized to repetitive treatment with low dose radiation (1 Gy) in the presence of the prodrug ganciclovir. It was therefore considered that the p21 gene promoter in combination with a rAAV vector is potentially usable for the development of a low-dose radiation-inducible vector for cancer gene therapy.
