Genetic and functional studies implicate HIF1α as a 14q kidney cancer suppressor gene.

Abstract

UNLABELLED:

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 HIF2α is a kidney cancer oncoprotein. In this article, we identify focal, homozygous deletions of the HIF1α locus on 14q in clear cell renal carcinoma cell lines. Wild-type HIF1α suppresses renal carcinoma growth, but the products of these altered loci do not. Conversely, downregulation of HIF1α in HIF1α-proficient lines promotes tumor growth. HIF1α activity is diminished in 14q-deleted kidney cancers, and all 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.

SIGNIFICANCE:

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 HIF1α is a target of 14q loss in kidney cancer.

• Authors: Chuan Shen, Rameen Beroukhim, Steven E Schumacher, Jing Zhou, Michelle Chang, Sabina Signoretti, William G Kaelin Jr
• Journal: Cancer discovery (Cancer Discov) Vol. 1 Issue 3 Pg. 222-35 (Aug 2011) ISSN: 2159-8290 [Electronic] United States
• PMID: 22037472 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit

Topics

• Animals
• Carcinoma, Renal Cell (genetics)
• Cell Line, Tumor
• Cell Proliferation
• Chromosomes, Human, Pair 14 (genetics)
• Genes, Tumor Suppressor
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (genetics)
• Kidney Neoplasms (genetics)
• Mice
• Mice, Nude
• Mutation (genetics)