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-1α mRNA 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-1α as 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.
Written by:
Vainrib M, Golan M, Amir S, Dang DT, Dang LH, Bar-Shira A, Orr-Urtreger A, Matzkin H, Mabjeesh NJ. Are you the author?
Department of Urology, Meir Medical Center, Kfar Saba, Israel.
Reference: Cancer Biol Ther. 2012 Jul 1;13(9).
doi: 10.4161/cbt.20554
PubMed Abstract
PMID: 22647679
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