Genetic and Functional Studies Implicate HIF1α as a 14q Kidney Cancer Suppressor Gene
Menée sur des lignées cellulaires de carcinome à cellules rénales, cette étude identifie le rôle de suppresseur de tumeurs joué par le facteur de transcription HIF1
Kidney cancers often delete chromosome 3p, spanning the VHL tumor suppressor gene, and chromosome 14q, which presumably harbors one or more tumor suppressor genes. pVHL inhibits the HIF transcription factor and HIF2α is a kidney cancer oncoprotein. Here we identify focal, homozygous, deletions of the HIF1α locus on 14q in clear cell renal carcinoma cell lines. Wild-type HIF1α, but not the products of these altered loci, suppress renal carcinoma growth. Conversely, downregulation of HIF1α in HIF1α-proficient lines promote tumor growth. HIF1α activity is diminished in 14q deleted kidney cancers and all of the somatic HIF1α mutations identified in kidney cancers tested to date are loss of function. Therefore HIF1α has the credentials of a kidney cancer suppressor gene.