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

doi:10.4161/cbt.20554

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 journal › Article › peer-review

22 Scopus citations

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 language	English
Pages (from-to)	720-726
Number of pages	7
Journal	Cancer Biology and Therapy
Volume	13
Issue number	9
DOIs	https://doi.org/10.4161/cbt.20554
State	Published - 1 Jul 2012
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

Molecular Medicine
Oncology
Pharmacology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.4161/cbt.20554

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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.",

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doi = "10.4161/cbt.20554",

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AU - Vainrib, Michael

AU - Golan, Maya

AU - Amir, Sharon

AU - Dang, Duyen T.

AU - Dang, Long H.

AU - Bar-Shira, Anat

AU - Orr-Urtreger, Avi

AU - Matzkin, Haim

AU - Mabjeesh, Nicola J.

N1 - 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’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.

PY - 2012/7/1

Y1 - 2012/7/1

N2 - 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.

AB - 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.

KW - C1772T

KW - Cancer

KW - Hypoxia-inducible factor-1α

KW - Polymorphism

KW - Prostate

KW - mRNA

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JF - Cancer Biology and Therapy

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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