The Wilms' tumor gene product, WT1, represses transcription of the platelet-derived growth factor A-chain gene

Abstract

The Wilms' tumor locus on chromosome 11p13 contains a tumor suppressor gene, wt1, which encodes a DNA binding protein (WT1) with four zinc fingers and a glutamine-proline-rich N terminus and which functions as a repressor of transcription. The platelet-derived growth factor (PDGF) A-chain gene encodes a potent growth factor, which is expressed in high levels in a number of tumor cell lines. We initiated a search for WT1 target genes and now report that WT1 strikingly represses transcription of the PDGF A-chain gene in transient transfection assays and that the WT1 protein interacts directly with a highly G+C-rich region of the PDGF A-chain promoter in gel mobility shift assays. The results suggest that WT1 may function to repress expression of the PDGF A-chain gene and that loss of this or related repressor activities may contribute to the abnormal growth of Wilms' tumors.