A region between-141 and-61 bp containing a proximal AP-1 is essential forconstitutive expression of urokinase-type plasminogen activator receptor

An 8.5-kb 5 '-flanking region of the human urokinase-type plasminogen activ ator receptor (uPAR) gene was cloned and the detailed uPAR promoter region defined in an 188-bp fragment between bases -141 and +47 relative to the tr anscription-start site. 5 '-Deletion to -100 and -60 in the region abolishe d its promoter activity, indicating that an 81-bp segment between - 141 and -61, which contains a proximal AP-I site at position -70, is required for uPAR promoter activity. Nuclear extracts from HCT116 cells contain proteins that specifically bind to the AP-I site. Mutation of the AP-1 motif reduce d uPAR promoter activity in comparison with the wild-types. Induction of uP AR expression by phorbol ester requires this AP-I motif in colon cancer cel ls. Cotransfection with the c-jun and c-fos expression vectors stimulated t he uPAR promoter activity four- to fivefold. These results demonstrate that the proximal AP-I motif is responsible for approximate to 50% of the basal expression of the uPAR gene.