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Identification of hypoxia‐inducible factor‐1α (HIF‐1α) polymorphism as a mutation in prostate cancer that prevents normoxia‐induced degradation by Xinyu S. Fu; Eunis Choi; Glenn J. Bubley; Steven P. Balk is a Medicine article available to read on EtoBox.

What is Identification of hypoxia‐inducible factor‐1α (HIF‐1α) polymorphism as a mutation in prostate cancer that prevents normoxia‐induced degradation about?

## Abstract ## BACKGROUND Hypoxia‐inducible factor‐1α (HIF‐1α) regulates cellular responses to hypoxia and is rapidly degraded under normoxia through von Hippel‐Lindau (VHL) mediated ubiquitination. Although HIF‐1α stabilization appears to be the molecular basis for VHL‐associated cancers, stabilizing mutations in HIF‐1α have not been reported. ## METHODS A series of 15 metastatic androgen independent prostate cancers were examined for mutations in the oxygen‐dependent domain (ODD) of HIF‐1α by PCR amplification and DNA sequencing. ## RESULTS A somatic proline to serine mutation in codon 582 (P582S) was identified in one sample. Transfection studies with a __HIF‐1α__ regulated reporter gene showed increased transcriptional activity that correlated with higher mutant HIF‐1α protein expression. Increased expression of the P582S mutant induced by iron chelation, which blocks proline hydroxylation of wild‐type HIF‐1α, was markedly attenuated. The mutant also showed increased stability under normoxic versus hypoxic conditions. ## CONCLUSION The P582S HIF‐1α is a stable variant and HIF‐1α mutation is a mechanism for enhancing HIF‐1α activity in human cancer. The recent identification of

Who reads Identification of hypoxia‐inducible factor‐1α (HIF‐1α) polymorphism as a mutation in prostate cancer that prevents normoxia‐induced degradation?

Author

Xinyu S. Fu; Eunis Choi; Glenn J. Bubley; Steven P. Balk

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley (ISSN 0270-4137)

Published

2005

Language

EN

Field

Medicine (Health Sciences)