Journal
PLOS ONE
Volume 10, Issue 5, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0128239
Keywords
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Categories
Funding
- Cancer Prevention & Research Institute of Texas (CPRIT) [HIRP100680, RP110444]
- Texas Emerging Technology Fund [300-9-1958]
- Robert A. Welch Foundation [E-0004]
- Swedish Cancer Fund
- Marie Curie Actions FP7-PEOPLE-COFUND via the VINNOVA programme Mobility for Growth [GROWTH 291795]
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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.
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