Tumor-specific transgene expression from the human telomerase reverse transcriptase promoter enables targeting of the therapeutic effects of the Bax gene to cancers

J. Gu, S. Kagawa, M. Takakura, S. Kyo, M. Inoue, J. A. Roth, B. Fang

Research output: Contribution to journalArticle

182 Citations (Scopus)

Abstract

Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase, which is highly active in immortalized cells and >85% of human cancers but is quiescent in most normal somatic cells. To test the feasibility of using the hTERT promoter to induce rumor-specific transgene expression in cancer gene therapy, we constructed an adenoviral vector expressing a LacZ reporter gene driven by the hTERT core promoter and evaluated its activity in vitro and in vivo. The hTERT promoter could drive high-level expression of LacZ in tumor cells but not in normal cells and normal mouse tissues. Using a binary adenoviral system that can induce Bax gene expression, we showed that induction of the Bax gene expression via the hTERT promoter elicited tumor-specific apoptosis in vitro, suppressed tumor growth in nude mice, and prevented the toxicity of the Bax gene in vitro and in vivo. Thus, the hTERT promoter is apparently a strong and tumor-selective promoter with potential application in targeted cancer gene therapy.

Original languageEnglish
Pages (from-to)5359-5364
Number of pages6
JournalCancer Research
Volume60
Issue number19
Publication statusPublished - Oct 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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