title: Malignant pleural mesothelioma-targeted CREBBP/EP300 inhibitory protein 1 promoter system for gene therapy and virotherapy.
abstract: 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.
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. FukazawaT@aol.com
authors.forename: Takuya
authors.initials: T
authors.lastname: Fukazawa
authors.forename: Junji
authors.initials: J
authors.lastname: Matsuoka
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Naomoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Maeda
authors.forename: Mary L
authors.initials: ML
authors.lastname: Durbin
authors.forename: Noriaki
authors.initials: N
authors.lastname: Tanaka