Malignant pleural mesothelioma-targeted CREBBP/EP300 inhibitory protein 1 promoter system for gene therapy and virotherapy

被引：14

作者：

Fukazawa, Takuya ^{[1
]}

Matsuoka, Junji ^{[1
]}

Naomoto, Yoshio ^{[1
]}

Maeda, Yutaka ^{[2
]}

Durbin, Mary L. ^{[3
]}

Tanaka, Noriaki ^{[1
]}

机构：

[1] Okayama Univ, Dept Surg Gastroenterol, Grad Sch Med Dent & Pharmaceut Sci, Okayama 7008558, Japan

[2] Cincinnati Childrens Hosp, Med Ctr, Div Pulm Biol, Cincinnati, OH USA

[3] Univ Calif Irvine, Dept Ecol & Evolut Biol, Irvine, CA 92717 USA

来源：

CANCER RESEARCH | 2008年 / 68卷 / 17期

关键词：

D O I：

10.1158/0008-5472.CAN-08-0047

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Gene therapy and virotherapy are one of the approaches used to treat malignant pleural mesothelioma. To improve the efficiency of targeting malignant mesothelioma cells-, we designed a novel system using the promoter of the CREBBP/EP300 inhibitory protein 1 (CRI1), a gene specifically expressed in malignant pleural mesothelioma. Four tandem repeats of the CRI1 promoter (CRI1(-138) (4x)) caused significantly high promoter activity in malignant pleural mesothelioma cells but little promoter activity in normal mesothelial cells and normal fibroblasts. The recombinant adenoviral vector expressing proapoptotic BH3-interacting death agonist or early region 1A driven by the CRI1(-138 4x) promoter induced cell death in malignant mesothelioma cells but not in normal cells. Moreover, these viruses showed antitumor effects in a mesothelioma xenograft mouse model. Here, we describe a novel strategy to target malignant mesothelioma using the CRI1(-138 4x) promoter system.

引用

页码：7120 / 7129

页数：10

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