Heat-inducible transgene expression with transcriptional amplification mediated by a transactivator

Akira Ito, Noriaki Okamoto, Masaki Yamaguchi, Kawabe Yoshinori, Masamichi Kamihira

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Purpose: Control of therapeutic gene expression in tumours is a major goal of gene therapy research, as it can restrict cytotoxic gene expression in cancer cells. In addition, the combination of hyperthermia with gene therapy through the application of heat-inducible vectors can result in considerable improvements in therapeutic efficiency. In this study, to combine heat-inducibility with high-level transgene expression, we developed a heat-inducible transgene expression system with transcriptional amplification mediated by a tetracycline-responsive transactivator. Materials and methods: A hybrid promoter was generated by placing the heat shock protein (HSP) 70B′ promoter under the tetracycline-repressor responsive element sequence, and a reporter/therapeutic gene expression plasmid was constructed by placing a reporter/therapeutic gene under the control of this hybrid promoter. Results: When the transactivator expression plasmid harbouring an expression cassette of the tetracycline-responsive transactivator gene was co-transfected with a reporter gene expression plasmid, the reporter gene expression was controlled by heat treatment. With this system, high levels of heat-induced transgene expression were observed compared to that from the HSP promoter alone without the transactivator. Evaluation of in vitro therapeutic effects using cancer cell lines revealed that therapeutic gene expression effectively caused cell death in a greater percentage of the cells. Conclusion: These findings indicate that this strategy improves the efficacy of cancer gene therapy.

Original languageEnglish
Pages (from-to)788-798
Number of pages11
JournalInternational Journal of Hyperthermia
Volume28
Issue number8
DOIs
Publication statusPublished - Dec 1 2012

Fingerprint

Trans-Activators
Transgenes
Hot Temperature
Reporter Genes
Gene Expression
Tetracycline
Genetic Therapy
Plasmids
Heat-Shock Proteins
Therapeutics
Neoplasms
Neoplasm Genes
Therapeutic Uses
Cell Death
Fever
Cell Line
Research
Genes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)
  • Cancer Research

Cite this

Heat-inducible transgene expression with transcriptional amplification mediated by a transactivator. / Ito, Akira; Okamoto, Noriaki; Yamaguchi, Masaki; Yoshinori, Kawabe; Kamihira, Masamichi.

In: International Journal of Hyperthermia, Vol. 28, No. 8, 01.12.2012, p. 788-798.

Research output: Contribution to journalArticle

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