Malignant Pleural Mesothelioma-Targeted CREBBP/EP300 Inhibitory Protein 1 Promoter System for Gene Therapy and Virotherapy

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 ma...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2008-09, Vol.68 (17), p.7120-7129
Main Authors: FUKAZAWA, Takuya, MATSUOKA, Junji, NAOMOTO, Yoshio, MAEDA, Yutaka, DURBIN, Mary L, TANAKA, Noriaki
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Biological and medical sciences
Blotting, Western
Cell Line, Tumor
Female
Flow Cytometry
Genetic Therapy
Humans
Medical sciences
Mesothelioma - genetics
Mesothelioma - therapy
Mice
Mice, Inbred BALB C
Mice, Nude
Nuclear Proteins - genetics
Oncolytic Virotherapy
Pharmacology. Drug treatments
Pleural Neoplasms - genetics
Pleural Neoplasms - therapy
Pneumology
Promoter Regions, Genetic
Repressor Proteins - genetics
Tumors
Tumors of the respiratory system and mediastinum
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-08-0047