Heat-inducible transgene expression system incorporating a positive feedback loop of transcriptional amplification for hyperthermia-induced gene therapy

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

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8 Citations (Scopus)

Abstract

One of the major goals of gene therapy is to regulate the expression of therapeutic genes in desired cells or tissues. For this purpose, heat-inducible vectors have been exploited for cancer gene therapy combined with hyperthermia, which can result in considerable improvement of therapeutic effects. In the present study, we constructed a novel heat-inducible gene expression system incorporating a transactivation system with a positive feedback loop of transcriptional amplification. The target gene expression mediated by the transactivator under the control of a heat shock protein 70B' promoter is enhanced by self-promoted transactivator gene expression. This expression system showed tight control of target gene expression together with high-level expression; enhanced expression of the reporter gene was observed in transfected cells upon heat treatment, while negligible gene expression was detected in non-heated cells. When a therapeutic gene was used as the target gene, a considerable cytotoxic effect was observed after heat treatment of cancer cells transfected with the plasmids. The heat-induced transgene expression system is a promising new approach for the development of both a safe and effective vector for hyperthermia-based cancer gene therapy.

Original languageEnglish
Pages (from-to)460-465
Number of pages6
JournalJournal of Bioscience and Bioengineering
Volume114
Issue number4
DOIs
Publication statusPublished - Oct 1 2012

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Gene therapy
Induced Hyperthermia
Transgenes
Gene expression
Genetic Therapy
Amplification
Hot Temperature
Feedback
Gene Expression
Genes
Trans-Activators
Neoplasm Genes
Heat treatment
Fever
Heat-Shock Proteins
Therapeutic Uses
Therapeutics
Reporter Genes
Plasmids
Transcriptional Activation

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

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abstract = "One of the major goals of gene therapy is to regulate the expression of therapeutic genes in desired cells or tissues. For this purpose, heat-inducible vectors have been exploited for cancer gene therapy combined with hyperthermia, which can result in considerable improvement of therapeutic effects. In the present study, we constructed a novel heat-inducible gene expression system incorporating a transactivation system with a positive feedback loop of transcriptional amplification. The target gene expression mediated by the transactivator under the control of a heat shock protein 70B' promoter is enhanced by self-promoted transactivator gene expression. This expression system showed tight control of target gene expression together with high-level expression; enhanced expression of the reporter gene was observed in transfected cells upon heat treatment, while negligible gene expression was detected in non-heated cells. When a therapeutic gene was used as the target gene, a considerable cytotoxic effect was observed after heat treatment of cancer cells transfected with the plasmids. The heat-induced transgene expression system is a promising new approach for the development of both a safe and effective vector for hyperthermia-based cancer gene therapy.",
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AU - Ito, Akira

AU - Okamoto, Noriaki

AU - Kawabe, Yoshinori

AU - Kamihira, Masamichi

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