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

Gene Ther. 1997 Oct;4(10):1045-52. doi: 10.1038/sj.gt.3300510.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology
  • Blotting, Northern
  • Cell Survival / drug effects
  • Ganciclovir / pharmacology
  • Gene Expression Regulation, Neoplastic*
  • Genes, erbB-2*
  • Genetic Therapy / methods
  • Genetic Vectors
  • Humans
  • Mucin-1 / genetics*
  • Prodrugs / metabolism*
  • Retroviridae / enzymology
  • Retroviridae / genetics
  • Simplexvirus / enzymology
  • Simplexvirus / genetics
  • Thymidine Kinase / metabolism*
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / enzymology

Substances

  • Antiviral Agents
  • Mucin-1
  • Prodrugs
  • Thymidine Kinase
  • Ganciclovir