Estrogen receptor β2 induces hypoxia signature of gene expression by stabilizing HIF-1α in prostate cancer

Prasenjit Dey, Laura A. Velazquez-Villegas, Michelle Faria, Anthony Turner, Philp Jonsson, Paul Webb, Cecilia Williams, Jan Åke Gustafsson, Anders M. Ström

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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.

Original languageEnglish (US)
Article numbere0128239
JournalPLoS ONE
Volume10
Issue number5
DOIs
StatePublished - May 26 2015

ASJC Scopus subject areas

  • General

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