Proto-oncogene N-myc promoter is down regulated by the Wilms' tumor suppressor gene WT1
Zhang, X.; Xing, G.; Saunders, G.F.
Anticancer Research 19(3a): 1641-1648
1999
ISSN/ISBN: 0250-7005 PMID: 10470095 Document Number: 506313
The Wilms' tumor 1 (WT1) gene is a tumor suppressor gene that encodes a zinc-finger transcription factor. WT1 represses transcription of several growth factors and growth factor receptors. The N-myc proto-oncogene encodes a transcription factor which regulates cell growth and differentiation. N-myc 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 WT1 (R394W) which has a mutation in the DNA binding domain could not repress the N-myc promoter. Electrophoretic mobility shift assays showed that the oligonucleotides containing the WT1 motifs could bind recombinant WT1 proteins. This suggests that the repression of the N-myc promoter is mediated through the WT1 binding sites. This finding may help to elucidate the relationship of WT1 and N-myc in tumorigenesis and renal development.