The suicide gene introduction using two recombinant adenovirus vectors with HER2 promoter and Cre/loxP system

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  • Maruyama Masateru
    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
  • Nodagashira Tatsuya
    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
  • Munakata Hirofumi
    Department of Pediatric Surgery, Hirosaki University

Bibliographic Information

Other Title
  • Cre/loxP システムを利用したアデノウィルス二重感染法による自殺遺伝子誘導

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Abstract

    We examined the therapeutic efficacy for the suicide gene introduction using two recombinant adenovirus vectors with HER2 promoter and Cre/loxP system in human gastric cancer cell lines, MKN-7 and MKN-28. HER2 protein level was more expressed in MKN-7 than in MKN-28. Next, we constructed a Cre recombinae expression vector in HER2-producing cell specifically, AxHER2NCre and AxCALNCD expressing cytosine deaminase (CD) gene under the control of the CAG promoter by the Cre switching system. Much higher CD messenger RNA (CD mRNA) and CD protein expression were induced in cells by the double infection method than by AxCALNCD only. Furthermore, CD mRNA and CD protein expression were induced higher in HER2-overexpressing cell line, MKN-7 than in MKN-28. We examined the efficacy of cell growth inhibition using 5-fluorocytosine (5-FC) as anti-tumor prodrug. Inhibition effect was dose-dependent at each cell line and rate was more in MKN-7 in comparison with MKN-28. This system can be applied for HER2-overexpressing cancer specific gene therapy.

Journal

  • Hirosaki Medical Journal

    Hirosaki Medical Journal 61 (2-4), 150-158, 2011

    Hirosaki University Graduate School of Medicine,Hirosaki Medical Society

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