Proto-oncogene N-myc promoter is down regulated by the Wilms' tumor suppressor gene WT1

The Wilms' tumor I (WT1) gene is it tumor suppressor gene that encodes a zi nc-finger transcription factor. WT1 represses transcription of several grow th factors and growth factor receptors. The N-myc proto-oncogene encodes a! transcription factor which regulates cell growth and differentiation. N-my c is coexpressed with WT1 in the developing kidney and is overexpressed in many Wilms' tumors,Here, we show that the proto-oncogene N-myc promoter was down-regulated by WT1 in transient transfection assays. However, mutant WT 1 (R394W) which has a mutation in the DNA binding domain could not repress the N-myc promoter. Electrophoretic mobility shift assays showed that the o ligonucleotides containing the WT1 motifs could bind recombinant WT1 protei ns. This suggests that the repression of the N-myc promoter is mediated thr ough the WT1 binding sites. This finding may help to elucidate the relation ship of WT1 and N-myc in tumorigenesis and renal development.