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Regulation of p21 gene promoter in response to clinically relevant doses of radiation
https://repo.qst.go.jp/records/62778
https://repo.qst.go.jp/records/6277837f50090-2a2d-4b9e-b954-6d3b6ef969d0
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2008-10-15 | |||||
| タイトル | ||||||
| タイトル | Regulation of p21 gene promoter in response to clinically relevant doses of radiation | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Nenoi, Mitsuru
× Nenoi, Mitsuru× 根井 充 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Tumor suppressor protein p53 is a transcription factor which plays important roles in biological responses to a wide range of ionizing radiation (IR) doses. Elucidation of the molecular mechanisms for its function after actually relevant doses of IR is therefore crucial for the accurate understanding of the biological effects of IR. p21WAF1 is one of the p53 target genes, functioning in cell cycle checkpoint regulation. In the present study, we performed a comprehensive analysis of the p21WAF1 gene promoter after the clinically relevant doses of IR with a sensitive reporter assay system, which we have recently established by use of recombinant adeno-associated virus (rAAV) vectors. It was shown that binding of a transcription factor Oct-1 to its recognition sequences at -1.1 kb and -1.8 kb was necessary to induce the p21WAF1 gene promoter. In addition, stable transfection of cells with the Oct-1-specific siRNA suppressed both the basal and the IR-inducible components of the p21WAF1 gene expression. These results demonstrate that Oct-1 plays a cooperative role in p53-mediated regulation of the p21WAF1 gene after irradiation. 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. Then, we investigated potential usability of the rAAV vector system in clinical application. 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 1 Gy of IR 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. | |||||
| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 21st International CODATA Conference | |||||
| 発表年月日 | ||||||
| 日付 | 2008-10-08 | |||||
| 日付タイプ | Issued | |||||
