TUMOR SUPPRESSION BY THE HUMAN VON HIPPEL-LINDAU GENE-PRODUCT

A partial cDNA sequence for the gene linked to the von Hippel-Lindau ( VHL) syndrome was reported in 1993. Mutation or loss of both VHL allel es has been documented in sporadic renal cell carcinomas and in the ne oplasms that arise in von Hippel-Lindau kindreds. We have determined t hat the protein product of the VHL gene is an approximately 30 kilodal ton cytoplasmic protein. The renal carcinoma cell line 786-0 is known to harbour a VHL mutation and, as shown here, fails to produce a wild- type VHL protein. Reintroduction of wild-type, but not mutant, VHL int o these cells had no demonstrable effect on their growth in vitro but inhibited their ability to form tumours in nude mice.