Efficient gene transduction in HER2-expressing cancer cells by two recombinant adenovirus vectors with HER2 promoter and Cre/loxP system

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  • Nodagashira Tatsuya
    Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine
  • Odagiri Hiroki
    Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine
  • Ikenaga Shojiro-Kazunori
    Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine
  • Maruyama Masaki
    Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine
  • Sato Toshiyuki
    Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine
  • Hakamada kenichi
    Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine

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Other Title
  • Cre/loxP system を用いた HER2/neu 発現細胞に対する特異的かつ効率的遺伝子導入システムの開発
  • Efficient Gene Transduction in HER2-Expressing Cells by Two Recombinant Adenovirus Vectors with HER2 Promotor and Cre/loxP System

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Abstract

    Tissue-specific promoter has been used for cancer-specific suicide gene therapy, but its transcriptional activity is relatively low. For more efficient gene therapy of HER2-expressing tumor, a double adenovirus infection system was established, in which a ‘regulator’ vector carried Cre gene under the control of HER2 promoter and ‘target’ vectors carried target genes activated by Cre. We constructed a Cre recombinase expression vector, AxHER2Cre, for the ‘regulator’ vector. By the combination of this vector and AxCALNLZ, β-D-galactosidase was induced in 90% and 70% of MKN7 and MDA-MB-453, HER2‒overexpressing cell lines, but only about 20% and 10% of MKN28 and MCF7, low HER2-expressing cell lines. By the quantification analysis, the β-galactosidase activities induced by this system were comparable to those by the combination of AxCANCre and AxCALNLZ. These results indicated that Cre/loxP system under the regulation of HER2 promoter could induce efficient gene expression, maintaining the HER2-expression specificity. Breast cancer with HER2 overexpression is treated with trastuzumab. However, refractory or resistance of HER2 positive breast cancer against trastuzumab becomes a severe clinical problem, recently. This system seemed to be another therapeutic option.

Journal

  • Hirosaki Medical Journal

    Hirosaki Medical Journal 61 (1), 26-34, 2010

    Hirosaki University Graduate School of Medicine,Hirosaki Medical Society

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