@misc{oai:repo.qst.go.jp:00067845,
 author = {Nenoi, Mitsuru and Daino, Kazuhiro and Ichimura, Sachiko and 根井 充 and 臺野 和広 and 沼田 幸子},
 month = {Aug},
 note = {For a cancer gene therapy, controled expression of anti-tumoric transgenes in the radiation field, by use of ionizing radiation-inducible promoters, is one of the approaches for the tumor-specific gene delivery. The most widely utilized promoter for this purpose is that of the early growth response 1 gene (Egr1). However induction of the Egr1 promoter requires relatively high doses of radiation. In contrast, tumor suppressor protein p53 is induced by lower doses of radiation, and activates transcription of its target genes. Nevertheless there has been only a limited number of reports showing utilization of p53-target gene promoter, such as that of the p21 gene, in vector development for cancer gene therapy. It is mainly because that the transfected promoter of p53-target genes is much less responsive to radiation than those of the endogenous p53-target genes. Recently plenty of evidences have been reported showing that association of p53 with its recognition sequence of DNA is dependent on chromatin structure. For the purpose of developing a low-dose radiation-responsive vector for cancer gene therapy, we investigated availability of a promoter of p53-target genes by examining if IR-response of the p21 gene promoter could be enhanced when integrated into chromosomes of host cells by use of rAAV vectors.
When a p21 gene promoter-driven reporter construct was transfected into a human breast cancer cell line MCF-7 by electroporation, radiation response was only 1.3-fold after 1 Gy and 1.1-fold after 0.5Gy. In contrast, the p21 gene promoter-driven reporter gene transduced by the adeno-associated virus vector was highly responsive to low-dose radiation being 2.1-fold after 1 Gy and 1.7-fold after 0.5 Gy. Radiation response of the p21 gene promoter transduced by the AAV vector was almost, 第10回日本遺伝子治療学会総会},
 title = {Development of a low-dose radiation-responsive vector},
 year = {2004}
}