Estrogen receptor β2 induces hypoxia signature of gene expression by stabilizing HIF-1α in prostate cancer Journal Article
| Authors: | Dey, P.; Velazquez-Villegas, L. A.; Faria, M.; Turner, A.; Jonsson, P.; Webb, P.; Williams, C.; Gustafsson, J. A.; Strom, A. M. |
| Article Title: | Estrogen receptor β2 induces hypoxia signature of gene expression by stabilizing HIF-1α in prostate cancer |
| 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. © 2015 Dey et al. |
| Keywords: | vasculotropin; controlled study; protein expression; unclassified drug; promoter region; nonhuman; animal cell; gene expression profiling; protein protein interaction; carcinogenesis; prostate cancer; hypoxia; gene expression regulation; messenger rna; microarray analysis; gene interaction; genetic stability; metastasis potential; bioinformatics; tumor vascularization; hypoxia inducible factor 1alpha; transcription factor twist; estrogen receptor beta; male; article; transcription factor twist1; estrogen receptor beta2; estrogen receptor beta5; erbeta2 gene; hif1alpha gene |
| Journal Title: | PLoS ONE |
| Volume: | 10 |
| Issue: | 5 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2015-05-26 |
| Start Page: | e0128239 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0128239 |
| PROVIDER: | scopus |
| PMCID: | PMC4444278 |
| PUBMED: | 26010887 |
| DOI/URL: | |
| Notes: | See Erratum, DOI: 10.1371/journal.pone.0132085 -- Article -- Export Date: 22 February 2016 -- Source: Scopus |
