Constitutive expression of the Wilms tumor suppressor gene (WT1) in renal cell carcinoma

The expression of the Wilms tumor suppressor gene WTI is largely restricted to elements of the developing urogenital system. In the fetal kidney, WTI transcripts are present at low levels in the condensing mesenchyme and at much higher levels in differentiating glomerular epithelium and are not detected in other mesenchymaloderived epithelial structures such as the proximal and distal tubules. However, WTI expression is observed in tubule-like elements found in some Wilms tumors. As renal cell carcinoma (RCC) of the clear cell type is one of the most prevalent adult tumors of the kidney, and is thought to originate from the epithelial cells of the proximal tubules, we studied WTI expression in RCCs. Despite the absence of WTI in normal primary epithelial cells derived from proximal tubules, RCC tumors and tumor-derived cell lines expressed WTI RNA. Immunocytochemical analyses of tumor cryosections showed widespread expression throughout the poorly differentiated epithelial components of the tumor. Immunoblots of RCC samples detected a normal size WTI protein and reciprocal antibody immunoprecipitations of RCC cell extracts indicated that WTI interacts with p53 as has been demonstrated for normal human fetal kidney. The aberrant expression of functional WTI in RCC may represent a reversion to a more dedifferentiated phenotype and may contribute to the tumorigenic phenotype by inappropriately activating or repressing genes involved in growth regulation.