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 22kDa in a 16-day-old fetal rat but only 20kDa protein in an adult rat. This is the first demonstration of VHL alteration at the protein level.
Shiao
Yih Horng
YH
Laboratory of Comparative Carcinogenesis, Building 538, Room 205, National Cancer Institute at Frederick, Frederick, MD 21702, USA. shiao@mail.ncifcrf.gov
Ramakrishna
Gayatri
G
Anderson
Lucy M
LM
Perantoni
Alan O
AO
Rice
Jerry M
JM
Diwan
Bhalchandra A
BA
D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D002273:Carcinogens; D004252:DNA Mutational Analysis; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics*; D004052:Diethylnitrosamine / Q000031:analogs & derivatives*; D015536:Down-Regulation; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D016133:Polymerase Chain Reaction; D051381:Rats; D011916:Rats, Inbred F344; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D009396:Wilms Tumor / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D006623:von Hippel-Lindau Disease / Q000235:genetics / Q000378:metabolism*
D002273:Carcinogens; D017931:DNA Primers; D004273:DNA, Neoplasm; D025521:Tumor Suppressor Proteins; C023845:N-ethyl-N-hydroxyethylnitrosamine; D004052:Diethylnitrosamine; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases