Abstract
In order to exploit differences in gene expression between normal and malignant cells for genetic prodrug-activation therapy, we have generated recombinant retroviruses containing the herpes simplex virus thymidine kinase coding region cloned downstream of sequences derived from the 5′-flanking regions of the MUC1 and ERBB2 genes. Transduction with retroviruses containing MUC1 promoters resulted in an increase in GCV sensitivity in MUC1-positive cells. A further increase in GCV sensitivity was achieved when MUC1-positive cells were transduced with retroviruses containing chimeric MUC1/ERBB2 promoters. No significant sensitization to GCV was observed when MUC1-negative cells were transduced with these recombinant retroviruses. These results suggest that one may be able to develop a tumour-selective therapy by utilizing the transcriptional regulatory regions of the MUC1 and ERBB2 genes to drive the expression of suicide genes.
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Ring, C., Blouin, P., Martin, LA. et al. Use of transcriptional regulatory elements of the MUC1 and ERBB2 genes to drive tumour-selective expression of a prodrug activating enzyme. Gene Ther 4, 1045–1052 (1997). https://doi.org/10.1038/sj.gt.3300510
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DOI: https://doi.org/10.1038/sj.gt.3300510
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