INHIBITION OF GENE-EXPRESSION FROM THE HUMAN C-ERBB GENE PROMOTER BY A RETROVIRAL VECTOR EXPRESSING ANTI-GENE RNA

Anti-gene is a potent inhibitor of transcriptional promoter activity a nd subsequent gene expression. This property has been exploited to sup press the expression of a variety of oncogenes for regulating tumor pr oliferation or viral activities. In this paper, we describe a novel re troviral vector designed to express human c-erbB anti-gene RNA and to reduce the promoter activity in the cells. Mouse fibroblast NIH3T3 cel ls were stably transfected with an expression construct containing a t runcated human c-erbB gene promoter fused to the firefly luciferase re porter gene. Infection into these cells of the c-erbB anti-gene retrov iral vector targeted to the 26 bp pyrimidine-rich element in the human c-erbB gene promoter resulted in a dose-dependent decrease in the luc iferase activity of the cells. Retroviral vector expressing anti-gene RNA may be useful as an alternative program of gene regulation in the cells. (C) 1997 Academic Press.