Down-regulation of von Hippel–Lindau protein in N-nitroso compound-induced rat non-clear cell renal tumors

Non-clear cell rat kidney tumors, inducible by N-nitroso compounds but lacking mutations in the von Hippel–Lindau (VHL) coding sequence, were examined for other VHL alterations. Neither mutations nor DNA methylation was detected in a putative promoter region. By immunohistochemistry, however, VHL protein level was evidently reduced in six of the eight eosinophilic renal epithelial tumors and in all the ten nephroblastomas. Immunoblotting of normal kidney detected two VHL proteins of 20 and 22 kDa in a 16-day-old fetal rat but only 20 kDa protein in an adult rat. This is the first demonstration of VHL alteration at the protein level.