@article{9174d32135894a8eb07206fe83b32f22,
title = "HIF1A C1772T polymorphism leads to HIF-1αmRNA overexpression in prostate cancer patients",
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.",
keywords = "C1772T, Cancer, Hypoxia-inducible factor-1α, Polymorphism, Prostate, mRNA",
author = "Michael Vainrib and Maya Golan and Sharon Amir and Dang, {Duyen T.} and Dang, {Long H.} and Anat Bar-Shira and Avi Orr-Urtreger and Haim Matzkin and Mabjeesh, {Nicola J.}",
note = "Funding Information: RNA isolation. Total RNA was extracted from cells using This work was supported by the Israel Cancer Association and Dr NucleoSpin RNA II kit (Macherey-Nagel) following the manu-Miriam and Sheldon G. Adelson Medical Research Foundation facturer{\textquoteright}s instructions. For total RNA isolation from patients, the (AMRF). sera were first treated with Erythrocyte lysis buffer (Qiagen, Inc.) and frozen at -80°C. After thawing, the sera were passed through QIAshredder columns (Qiagen) and then RNA was extracted as described above.",
year = "2012",
month = jul,
doi = "10.4161/cbt.20554",
language = "אנגלית",
volume = "13",
pages = "720--726",
journal = "Cancer Biology and Therapy",
issn = "1538-4047",
publisher = "Taylor and Francis Ltd.",
number = "9",
}