HIF1A C1772T polymorphism leads to HIF-1αmRNA overexpression in prostate cancer patients

Michael Vainrib, Maya Golan, Sharon Amir, Duyen T. Dang, Long H. Dang, Anat Bar-Shira, Avi Orr-Urtreger, Haim Matzkin, Nicola J. Mabjeesh

Research output: Contribution to journalArticlepeer-review

Abstract

Hypoxia-inducible factor 1α (HIF-1α) gene polymorphisms have been investigated for a possible role in mediating genetic predisposition to cancer. Our previous data show that men homozygous to C1772T polymorphism had 4-fold risk to develop prostate cancer. Therefore, we studied the effects of C1772T polymorphism on HIF-1α expression. HIF-1αmRNA expression levels were significantly higher in peripheral blood leukocytes of prostate cancer patients with the TT genotype compared with the CC genotype. Expression of C1772T HIF-1α in HIF-1α knockout cancer cells showed higher expression levels and stabilization of HIF-1α mRNA compared with the wild-type. Mutated HIF-1α protein half-life was similar to that of the wild-type. Hence, our data provide evidence that C1772T polymorphism causes activation of HIF-1αas a gain-of-function mechanism driven by stabilization of HIF-1α mRNA. These findings may also explain the increased risk of men homozygous to this mutation to develop prostate cancer.

Original languageEnglish
Pages (from-to)720-726
Number of pages7
JournalCancer Biology and Therapy
Volume13
Issue number9
DOIs
StatePublished - Jul 2012
Externally publishedYes

Keywords

  • C1772T
  • Cancer
  • Hypoxia-inducible factor-1α
  • Polymorphism
  • Prostate
  • mRNA

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