Use of transcriptional regulatory elements of the MUC1 and ERBB2 genes to drive tumour-selective expression of a prodrug activating enzyme

Ring, Christopher J. and Blouin, P. and Martin, L. A. and Hurst, H. C. and Lemoine, N. R. (1997) Use of transcriptional regulatory elements of the MUC1 and ERBB2 genes to drive tumour-selective expression of a prodrug activating enzyme. Gene therapy, 4 (10). pp. 1045-1052. ISSN 0969-7128

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Official URL: http://www.nature.com/gt/journal/v4/n10/pdf/330051...

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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.

Item Type:Article
Research Areas:Middlesex University Schools and Centres > School of Science and Technology > Natural Sciences
Citations on ISI Web of Science:43
ID Code:3313
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Deposited On:03 Dec 2009 09:07
Last Modified:24 Nov 2014 13:47

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