UI - 12086755
AU - Reeve AE; Becroft DM; Morison IM; Fukuzawa R
Insulin-like growth factor-II imprinting in cancer.
SO - Lancet 2002 Jun 15;359(9323):2050-1
AD - Cancer Genetics Laboratory, Department of Biochemistry, University of
Otago, Dunedin, New Zealand. firstname.lastname@example.org
UI - 12082525
AU - Sim EU; Smith A; Szilagi E; Rae F; Ioannou P; Lindsay MH; Little MH
Wnt-4 regulation by the Wilms' tumour suppressor gene, WT1.
SO - Oncogene 2002 May 2;21(19):2948-60
AD - Institute for Molecular Bioscience, The University of Queensland, St
Lucia, Brisbane, QLD 4072, Australia.
The Wilms' tumour suppressor gene, WT1, encodes multiple nuclear protein
isoforms, all containing four C-terminal zinc finger motifs. WT1
proteins can both activate and repress putative target genes in vitro,
although the in vivo relevance of these putative target genes is often
unverified. WT1 mutations can result in Wilms' tumour and the
Denys-Drash Syndrome (DDS) of infantile nephropathy, XY
pseudohermaphroditism and predisposition to Wilms' tumour. We have
established stable transfectants of the mouse mesonephric cell line,
M15, which express WT1 harbouring a common DDS point mutation (R394W). A
comparison of the expression profiles of M15 and transfectant C2A was
performed using Nylon-based arrays. Very few genes showed differential
expression. However Wnt-4, a member of the Wnt gene family of secreted
glycoproteins, was downregulated in C2A and other similar clones.
Doxycycline induction of WT1-A or WT1-D expression in HEK293 stable
transfectants also elicited an elevation in Wnt4 expression. Wnt4 is
critical for the mesenchyme-to-epithelial transition during kidney
development, making it an attractive putative WT1 target. We have mapped
human Wnt-4 gene to chromosome 1p35-36, a region of frequent LOH in WT,
have characterized the genomic structure of the human Wnt-4 gene and
isolated 9 kb of immediate promoter. While several potential WT1 binding
sites exist within this promoter, reporter analysis does not strongly
support the direct regulation of Wnt4 by WT1. We propose that Wnt-4
regulation by WT1 occurs at a more distant promoter or enhancer site, or
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