Proto-oncogene N-myc promoter is down regulated by the Wilms' tumor suppressor gene WT1.
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.
Zhang
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Department of Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Xing
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Saunders
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D001665:Binding Sites; D001859:Bone Neoplasms / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D016384:Consensus Sequence; D003587:Cytomegalovirus / Q000235:genetics; D004268:DNA-Binding Proteins / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D016162:Genes, Wilms Tumor; D016259:Genes, myc; D006801:Humans; D007668:Kidney / Q000196:embryology; D012516:Osteosarcoma / Q000473:pathology; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000502:physiology; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D025721:WT1 Proteins; D009396:Wilms Tumor / Q000235:genetics; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D020033:Protein Isoforms; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors; D025721:WT1 Proteins