Efficient Gene Transduction in HER2-Expressing Cells by Two Recombinant Adenovirus Vectors with HER2 Promotor and Cre/loxP System

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　Tissue-specifi c promoter has been used for cancer-specifi c suicide gene therapy, but its transcriptionalactivity is relatively low. For more effi cient gene therapy of HER2-expressing tumor, a double adenovirus infectionsystem 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, forthe ‘regulator’ vector. By the combination of this vector and AxCALNLZ, β-D-galactosidase was induced in 90% and70% 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 quantifi cation analysis, the β-galactosidase activities induced by this systemwere 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 effi cient gene expression, maintaining the HER2-expression specifi city. Breast cancer with HER2 overexpression is treated with trastuzumab. However, refractoryor resitance of HER2 positive breast cancer against trastuzumab becomes a severe clinical problem, recently. Thissystem seemed to be another therapeutic option.