Paired box gene expression in Wilms' tumor.

Wilms' tumor (WT) is an embryonal renal neoplasm with features resembling fetal kidney development. A family of genes potentially involved in WT induction is called the paired box (PAX) gene family. In this study we examined by Northern blot analysis the expression of several PAX genes in a variety of WTs and other childhood neoplasms. RNA was isolated from four primary WTs and 12 WTs propagated in nude mice (heterotransplant), as well as from a variety of other childhood renal and nonrenal embryonal tumors. RNA samples were electrophoretically separated in 1.2% agarose gels, transferred to nylon membranes, and hybridized to random primer-labeled PAX2, PAX8, and WT1 probes. Membranes were then exposed to x-ray films at -70 degrees C with intensifying screens. PAX2 and WT-1 expression were seen in all four primary WTs; PAX8 was seen in three of the four primary WTs. Of the 12 heterotransplant Wilms' tumors, PAX2, PAX8, and WT1 were concomitantly expressed in seven tumors. Another heterotransplant WT expressed WT1 alone. Expression of these three genes, with one exception, was not seen in the other childhood renal and nonrenal solid tumors. The PAX genes are transcriptional regulators; their protein products bind to specific DNA segments and control gene expression. Their role in the pathogenesis of Wilms' tumor and their interaction with WT1 are unclear. Elucidation of the functional significance of the PAX genes will provide important insights into not only the pathogenesis of WT but also the molecular control of the developing kidney.