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

Maruyama Masateru, Odagiri Hiroki, Ikenaga Shojiro-Kazunori, Nodagashira Tatsuya, Sato Toshiyuki, Hakamada Kenichi, Munakata Hirofumi

doi:10.32216/hirosakiigaku.61.2-4_150

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.

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

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