July 31, 1992Science
Repression of the Insulin-Like Growth Factor II Gene by the Wilms Tumor Suppressor WT1
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Discussion
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Implication
Molecular assays demonstrate WT1 represses IGF-II transcription via promoter binding, indicating a mechanism for growth factor overexpression in Wilms tumors.
Key Points
- Determine whether and how the tumor suppressor protein WT1 regulates transcription of the fetal growth factor gene insulin-like growth factor II (IGF-II).
- Mapped the major fetal IGF-II promoter using transient transfection assays spanning nucleotides -295 to +135 relative to the transcription start site.
- Evaluated WT1 binding affinities and transcriptional repression across multiple sites flanking the IGF-II transcriptional initiation site in vivo.
- Identified the core fetal IGF-II promoter within a region spanning nucleotides -295 to +135 from the transcription start site.
- Showed WT1 binds multiple promoter elements and potently represses IGF-II transcription in vivo, with maximal repression requiring binding sites flanking both sides of the initiation site.
Cite This Study
Drummond et al. (1992) studied this question.