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23 April 2024 |
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Repression of the insulin-like growth factor II gene by the Wilms tumor suppressor WT1 | | I A Drummond
; S L Madden
; P Rohwer-Nutter
; G I Bell
; V P Sukhatme
; F J Rauscher
; | | Date: |
31 Jul 1992 | | Journal: | Science, 257 (5070), 674-8 | | Abstract: | The Wilms tumor suppressor gene wt1 encodes a zinc finger DNA binding protein, WT1, that functions as a transcriptional repressor. The fetal mitogen insulin-like growth factor II (IGF-II) is overexpressed in Wilms tumors and may have autocrine effects in tumor progression. The major fetal IGF-II promoter was defined in transient transfection assays as a region spanning from nucleotides -295 to +135, relative to the transcription start site. WT1 bound to multiple sites in this region and functioned as a potent repressor of IGF-II transcription in vivo. Maximal repression was dependent on the presence of WT1 binding sites on each side of the transcriptional initiation site. These findings provide a molecular basis for overexpression of IGF-II in Wilms tumors and suggest that WT1 negatively regulates blastemal cell proliferation by limiting the production of a fetal growth factor in the developing vertebrate kidney. | | Source: | PubMed, pmid1323141 | | Services: | Forum | Review | Favorites | |
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