EXPRESSION OF WT1 PROTEIN IN FETAL KIDNEYS AND WILMS-TUMORS

BACKGROUND: Wilms' tumors are embryonic kidney neoplasms believed to r esult from a perturbation in the development of the metanephric blaste ma. A candidate gene (WT1) has been cloned that has been found to be m utated in a number of Wilms' tumors, consistent with its suggested rol e as a tumor suppressor gene. This gene has been shown to be essential to the normal development of the embryonic kidney. EXPERIMENTAL DESIG N: The aim of the present study was to provide information on the leve l at which the WT1 gene is regulated. Immunohistochemistry, immunofluo rescence, and in situ hybridization was used to examine the localizati on of WT1 protein and mRNA, respectively. We further used immunofluore scence to examine the WT1 expression in seven Wilms' tumors. RESULTS: In fetal kidneys, WT1 transcripts were detected with increasing levels of hybridization signal in induced blastemal cells, renal vesicles, p re-podocytes of comma- and S-shaped bodies, and podocytes of glomeruli . WT1 protein, detected by an antibody raised against recombinant WT1 fusion protein, was seen in the nuclei of the same cell types mentione d above, and the staining intensity was comparable to the levels of WT 1 transcripts. Immunostaining of seven Wilms tumors demonstrated that WT1 protein was expressed only in neoplastic structures whose normal c ounterparts also expressed WT1 protein. Neither stromal cells nor rhab domyoblasts contained WT1 protein. CONCLUSIONS: The results show that in fetal kidney, WT1 transcripts and protein are coordinately expresse d, and strongly associated with differentiation of metanephric blastem al cells into epithelial cells. Furthermore, the finding that WT1 tran scripts and protein are coordinately expressed, suggests that WT1 gene expression is primarily regulated at the level of transcription.