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Mutant mouse p53 transgene elevates the chemical induction of tumors that respond to gene silencing with siRNA
https://repo.qst.go.jp/records/45732
https://repo.qst.go.jp/records/45732c08417d6-eba9-4666-9891-5e88cf9c0eca
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2010-01-19 | |||||
タイトル | ||||||
タイトル | Mutant mouse p53 transgene elevates the chemical induction of tumors that respond to gene silencing with siRNA | |||||
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_6501 | |||||
資源タイプ | journal article | |||||
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 |
Tanooka, Hiroshi
× Tanooka, Hiroshi× Tatsumi, Kouichi× Tsuji, Hideo× Noda, Yuko× Katsube, Takanori× Ishii, Hiroko× Ootsuyama, Akira× et.al× 田ノ岡 宏× 巽 紘一× 辻 秀雄× 野田 攸子× 勝部 孝則× 石井 洋子× 大津山 彰 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | To study the role of mutant p53 in the induction and cure of tumors, we generated transgenic mice carrying mutant p53 (mp53)containing a 9 bp deletion in exon 6 in addition to wild-type p53, expressing both p53 and mp53. The mp53 cDNA was clonedfrom a radiation-induced mouse tumor and ligated to the chicken b-actin promoter/CMV-IE enhancer in the expression vector. Thepresence of mp53 suppressed p21 expression in primary fibroblasts after ionizing irradiation, indicating the dominant-negativeactivity of mp53 in the mice. These mice developed fibrosarcomas after the subcutaneous injection of 3-methylcholanthrene with an incidence 1.7-fold higher than that of wild-type mice (42% excess). The tumors were then treated via a potent atelocollagen delivery system with small interfering RNA (siRNA), that targeted the promoter/enhancer of the expression vector, resulting in the suppression of tumor growth in 30% of 44 autochthonous tumors, including four cures, and their transplants, the total fraction corresponding to the tumor excess. This suppressive effect involved the induction of apoptosis. These results indicate that mp53 activity causes tumors that can be suppressed by subsequent silencing of mp53 in the presence of wild-type p53 alleles. Cancer Gene Therapy (2009) 0, 000–000. doi:10.1038/cgt.2009.43 |
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書誌情報 |
Cancer Gene Therapy 巻 17, 号 1, p. 1-10, 発行日 2009-06 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0929-1903 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1038/cgt.2009.43 |