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PLoS One. 2015 May 26;10(5):e0128239. doi: 10.1371/journal.pone.0128239. eCollection 2015.

Estrogen Receptor β2 Induces Hypoxia Signature of Gene Expression by Stabilizing HIF-1α in Prostate Cancer.

Author information

1
University of Houston, Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, 3605 Cullen Boulevard, Science & Engineering Research Center, Bldg 545, Houston, Texas 77204-5056, United States of America.
2
Genomic Medicine Program, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, TX 77030, United States of America.
3
University of Houston, Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, 3605 Cullen Boulevard, Science & Engineering Research Center, Bldg 545, Houston, Texas 77204-5056, United States of America; Science for Life Laboratory, Department of Proteomics and Nanotechnology, KTH-Royal Institute of Technology, 171 21 Stockholm, Sweden.
4
University of Houston, Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, 3605 Cullen Boulevard, Science & Engineering Research Center, Bldg 545, Houston, Texas 77204-5056, United States of America; Department of BioSciences and Nutrition, Karolinska Institutet, Novum, S-141 57 Huddinge, Sweden.

Abstract

The estrogen receptor (ER) β variant ERβ2 is expressed in aggressive castration-resistant prostate cancer and has been shown to correlate with decreased overall survival. Genome-wide expression analysis after ERβ2 expression in prostate cancer cells revealed that hypoxia was an overrepresented theme. Here we show that ERβ2 interacts with and stabilizes HIF-1α protein in normoxia, thereby inducing a hypoxic gene expression signature. HIF-1α is known to stimulate metastasis by increasing expression of Twist1 and increasing vascularization by directly activating VEGF expression. We found that ERβ2 interacts with HIF-1α and piggybacks to the HIF-1α response element present on the proximal Twist1 and VEGF promoters. These findings suggest that at least part of the oncogenic effects of ERβ2 is mediated by HIF-1α and that targeting of this ERβ2 - HIF-1α interaction may be a strategy to treat prostate cancer.

PMID:
26010887
PMCID:
PMC4444278
DOI:
10.1371/journal.pone.0128239
[Indexed for MEDLINE]
Free PMC Article

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