E-cadherin is a WT1 target gene

The WT1 tumor suppressor gene encodes a transcription factor that can activ ate and repress gene expression. Transcriptional targets relevant for the g rowth suppression functions of WT1 are poorly understood. We found that mes enchymal NIH 3T3 fibroblasts stably expressing WT1 exhibit growth suppressi on and features of epithelial differentiation including up-regulation of E- cadherin mRNA. Acute expression of WT1 in NIH 3T3 fibroblasts after retrovi ral infection induced murine E-cadherin expression. In transient transfecti on experiments, the human and murine E-cadherin promoters were activated by co-expression of WT1. E-cadherin promoter activity was increased in cells overexpressing WT1 and was blocked by a dominant negative form of WT1. WT1 activated the murine E-cadherin promoter through a conserved GC-rich sequen ce similar to an EGR-1 binding site as well as through a CAAT box sequence. WT1 produced in vitro or derived from nuclear extracts bound to the WT1-re sponse element within the murine E-cadherin promoter, but not the CAAT box. E-cadherin, a gene important in epithelial differentiation and neoplastic transformation, represents a downstream target gene that links the roles of the WT1 in differentiation and growth control.