Increased expression of the insulin-like growth factor I receptor gene, IGF1R, in Wilms tumor is correlated with modulation of IGF1R promoter activity by the WT1 Wilms tumor gene product.

摘要: Abstract Wilms tumor is a pediatric neoplasm that arises from the metanephric blastema. The expression of gene encoding insulin-like growth factor II (IGF-II) often elevated in these tumors. Since many actions IGF-II are mediated through activation IGF-I receptor (IGF-IR), we have measured levels IGF-IR mRNA normal kidney and Wilms samples using solution hybridization/RNase protection assays. tumors were 5.8-fold higher than adjacent tissue. Among themselves, those containing heterologous stromal elements 2-fold (P < 0.01) without elements. (designated IGF1R) was inversely correlated with suppressor WT1, whose inactivation appears to be key step etiology tumor. Cotransfection Chinese hamster ovary cells rat human promoter constructs driving luciferase reporter genes WT1 vectors showed active product represses activity dose-dependent manner. These results suggest underexpression, deletion, or mutation may result increased IGF-IR, by an important aspect biology