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Estrogen Receptor beta 2 Induces Hypoxia Signature of Gene Expression by Stabilizing HIF-1 alpha in Prostate Cancer
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2015 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 10, no 5, e0128239Article in journal (Refereed) Published
Abstract [en]

The estrogen receptor (ER) beta variant ER beta 2 is expressed in aggressive castration-resistant prostate cancer and has been shown to correlate with decreased overall survival. Genome-wide expression analysis after ER beta 2 expression in prostate cancer cells revealed that hypoxia was an overrepresented theme. Here we show that ER beta 2 interacts with and stabilizes HIF-1 alpha protein in normoxia, thereby inducing a hypoxic gene expression signature. HIF-1 alpha is known to stimulate metastasis by increasing expression of Twist1 and increasing vascularization by directly activating VEGF expression. We found that ER beta 2 interacts with HIF-1 alpha and piggybacks to the HIF-1 alpha response element present on the proximal Twist1 and VEGF promoters. These findings suggest that at least part of the oncogenic effects of ER beta 2 is mediated by HIF-1 alpha and that targeting of this ER beta 2 -HIF-1 alpha interaction may be a strategy to treat prostate cancer.

Place, publisher, year, edition, pages
2015. Vol. 10, no 5, e0128239
Keyword [en]
Tumor-Suppressor Protein, Hippel-Lindau Protein, Androgen Receptor, Er-Beta, Alpha, Growth, Hif, Transcription, Metastasis, Mechanism
National Category
Biological Sciences Medical and Health Sciences
URN: urn:nbn:se:kth:diva-169966DOI: 10.1371/journal.pone.0128239ISI: 000355183900212PubMedID: 26010887ScopusID: 2-s2.0-84930221880OAI: diva2:826509
Swedish Cancer SocietyEU, FP7, Seventh Framework Programme, GROWTH 291795Science for Life Laboratory - a national resource center for high-throughput molecular bioscience

QC 20150625

Available from: 2015-06-25 Created: 2015-06-25 Last updated: 2015-06-25Bibliographically approved

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Williams, Cecilia
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Proteomics and NanobiotechnologyScience for Life Laboratory, SciLifeLab
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