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Truncation of WT1 results in downregulation of cyclin G1 and IGFBP-4 expression

K J Wagner1, C E Patek, C Miles

  • 1Sir Alastair Currie CRC Laboratories, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom.

Biochemical and Biophysical Research Communications
|September 28, 2001
PubMed

Insights

WT1 gene mutations are linked to Wilms' tumours. This study identified two new WT1 target genes, cyclin G1 and IGFBP4, by disrupting the WT1 gene's DNA-binding region in cells.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Wilms' tumour is associated with mutations in the WT1 gene.
  • The WT1 gene encodes a zinc finger transcription factor with numerous proposed target genes.
  • Understanding WT1's transcriptional targets is crucial for comprehending its role in development and disease.

Purpose of the Study:

  • To identify novel WT1 transcriptional targets.
  • To investigate the function of WT1 by examining gene expression in cells with disrupted WT1 DNA-binding domains.

Main Methods:

  • Gene targeting was used to create cell lines with truncated WT1 proteins lacking DNA-binding activity.
  • cDNA macroarrays were employed to analyze gene expression profiles in these modified cells.

Main Results:

  • Two novel WT1 transcriptional targets were identified: cyclin G1 (Ccng1) and insulin-like growth factor binding protein 4 (Igfbp4).
  • The expression of Ccng1 and Igfbp4 was found to be regulated by WT1.

Conclusions:

  • Cyclin G1 and IGFBP4 are suggested as new direct or indirect transcriptional targets of WT1.
  • These findings contribute to a better understanding of WT1 gene function and its role in associated disorders.

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