@misc{oai:repo.qst.go.jp:00063583,
 author = {Nenoi, Mitsuru and Bing, Wang and Nakajima, Tetsuo and 根井 充 and 王 冰 and 中島 徹夫},
 month = {Nov},
 note = {Accumulating evidences show that p53 plays important roles in biological responses to low-dose of ionizing radiation (IR). As p53 is a transcription factor, it is essential to elucidate the molecular mechanisms of its target gene transactivation with the aim of accurate understanding the biological effects of low-dose radiation. p21WAF1 is transcriptionally induced after exposure to IR depending on p53, and is involved in cell cycle checkpoint regulation. We performed a comprehensive analysis of the p21WAF1 gene promoter after irradiation with 0.2-2.0 Gy. The sensitive reporter assay system, which we have recently established by use of recombinant adeno-associated virus (rAAV) vectors, was effectively utilized. It was demonstrated that binding of Oct-1 to the sites at –1.1 kb and –1.75 kb as well as binding of p53 at –1.4 kb site, which contains only one and a half repeats of the p53 consensus sequence, are necessary for regulation of the p21WAF1 gene promoter. Functional involvement of Oct-1 was confirmed by use of Oct-1-specific siRNA which suppressed both the basal and the IR-inducible components of the p21WAF1 gene expression. We further considered the usability of the rAAV vector system in clinical application. In cancer gene therapy, restriction of antitumor transgene expression in a radiation field by use of IR-inducible promoters is one of the promising approaches for tumor-specific gene delivery. When tumor cells were transduced with the p21WAF1 gene promoter-driven HSVtk gene by rAAV vector, we found that the cells were significantly sensitized to repetitive treatment with low dose IR (1 Gy) in the presence of the prodrug ganciclovir. It was therefore considered that the p21WAF1 gene promoter in combination with a rAAV vector is of potential application to the development of a low-dose IR-inducible vector for cancer gene therapy., New Nuclear Research Symposium "Biological Responses to Low Dose Radiation"},
 title = {Regulation of p21WAF1 gene promoter in response to low to clinically relevant doses of radiation},
 year = {2008}
}