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

Takuya Fukazawa, Junji Matsuoka, Yoshio Naomoto, Yutaka Maeda, Mary L. Durbin, Noriaki Tanaka

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

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 CRI-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 CRI-138 4x promoter system.

Original languageEnglish
Pages (from-to)7120-7129
Number of pages10
JournalCancer Research
Volume68
Issue number17
DOIs
Publication statusPublished - Sep 1 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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