Genetic and functional studies implicate HIF1? as a 14q kidney cancer suppressor gene.

ABSTRACT: Kidney cancers often delete chromosome 3p, spanning the VHL tumor suppressor gene, and chromosome 14q, which presumably harbors ? 1 tumor suppressor genes. pVHL inhibits the hypoxia-inducible transcription factor (HIF), and HIF2? is a kidney cancer oncoprotein. In this article, we identify focal, homozygous deletions of the HIF1? locus on 14q in clear cell renal carcinoma cell lines. Wild-type HIF1? suppresses renal carcinoma growth, but the products of these altered loci do not. Conversely, downregulation of HIF1? in HIF1?-proficient lines promotes tumor growth. HIF1? activity is diminished in 14q-deleted kidney cancers, and all somatic HIF1? mutations identified in kidney cancers tested to date are loss of function. Therefore, HIF1? has the credentials of a kidney cancer suppressor gene.Deletion of 14q is a frequent event in clear cell renal carcinoma and portends a poor prognosis. In this study, we provide genetic and functional evidence that HIF1? is a target of 14q loss in kidney cancer.

SUBMITTER: Shen C 

PROVIDER: S-EPMC3202343 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature