Immunoprecipitation of DPD cellular lysates with anti-WT1 antibody revealed formation of WT1 repressor complexes containing Polycomb group proteins, enhancer of zeste homolog 2, menin, and DNA methyltransferase (DNMT1), whereas silencing of either WT1 or DNMT1 disrupted this complex with enhanced expression of PAX2.
In addition, the average numbers of double-positive cells for X-gal/Pax8, nestin/Pax8 and podocalyxin/Pax2 staining in the FSGS mice were comparable, whereas those of WT1/claudin1 were significantly increased.
We show that one of these target genes, calcineurin A-binding protein (CnABP), is coexpressed with Pax2 during kidney development and is overexpressed in >70% of WT samples analyzed.
We demonstrate abundant PAX3 and absence of PAX2 expression in a novel cell line (WitP3) isolated from the stromal portion of a WT bearing a homozygous deletion of the WT1 gene.
We therefore hypothesized that identification and characterization of the genes regulated by PAX2 may improve our understanding of developmentally related malignancies including WT.
Possible regulation of Wilms' tumour gene 1 (WT1) expression by the paired box genes PAX2 and PAX8 and by the haematopoietic transcription factor GATA-1 in human acute myeloid leukaemias.
Unlike the classic triphasic Wilms' tumor that contains blastema, stroma, and epithelial tubules, the anaplastic tumor expressed only marginal levels of insulin-like growth factor 2 (IGF-2) mRNA and imperceptible levels of the Wilms' tumor gene (WT-1), Pax-2, and Pax-8 mRNA.
By somatic cell hybrid mapping, the PAX2 gene was localized to chromosome 10q22.1-q24.3, although this region has not previously been implicated in Wilms' tumor.