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Breast Cancer Research
Published in: Breast Cancer Research 2/2011

Open Access 01-04-2011 | Research article

Estrogen receptor beta inhibits transcriptional activity of hypoxia inducible factor-1 through the downregulation of arylhydrocarbon receptor nuclear translocator

Authors: Wonchung Lim, Yeomyung Park, Jungyoon Cho, Choa Park, Joonwoo Park, Young-Kwon Park, Hyunsung Park, YoungJoo Lee

Published in: Breast Cancer Research | Issue 2/2011

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Abstract

Introduction

Estrogen receptor (ER) β is predicted to play an important role in prevention of breast cancer development and metastasis. We have shown previously that ERβ inhibits hypoxia inducible factor (HIF)-1α mediated transcription, but the mechanism by which ERβ works to exert this effect is not understood.

Methods

Vascular endothelial growth factor (VEGF) was measured in conditioned medium by enzyme-linked immunosorbent assays. Reverse transcription polymerase chain reaction (RT-PCR), Western blotting, immunoprecipitation, luciferase assays and chromatin immunoprecipitation (ChIP) assays were used to ascertain the implication of ERβ on HIF-1 function.

Results

In this study, we found that the inhibition of HIF-1 activity by ERβ expression was correlated with ERβ's ability to degrade aryl hydrocarbon receptor nuclear translocator (ARNT) via ubiquitination processes leading to the reduction of active HIF-1α/ARNT complexes. HIF-1 repression by ERβ was rescued by overexpression of ARNT as examined by hypoxia-responsive element (HRE)-driven luciferase assays. We show further that ERβ attenuated the hypoxic induction of VEGF mRNA by directly decreasing HIF-1α binding to the VEGF gene promoter.

Conclusions

These results show that ERβ suppresses HIF-1α-mediated transcription via ARNT down-regulation, which may account for the tumour suppressive function of ERβ.
Appendix
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Metadata
Title
Estrogen receptor beta inhibits transcriptional activity of hypoxia inducible factor-1 through the downregulation of arylhydrocarbon receptor nuclear translocator
Authors
Wonchung Lim
Yeomyung Park
Jungyoon Cho
Choa Park
Joonwoo Park
Young-Kwon Park
Hyunsung Park
YoungJoo Lee
Publication date
01-04-2011
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 2/2011
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2854

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