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.
authors.affiliation: 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.
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Dey
authors.affiliation: 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.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Velazquez-Villegas
authors.affiliation: 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.
authors.forename: Michelle
authors.initials: M
authors.lastname: Faria
authors.affiliation: 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.
authors.forename: Anthony
authors.initials: A
authors.lastname: Turner
authors.affiliation: 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.
authors.forename: Philp
authors.initials: P
authors.lastname: Jonsson
authors.affiliation: Genomic Medicine Program, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, TX 77030, United States of America.
authors.forename: Paul
authors.initials: P
authors.lastname: Webb
authors.affiliation: 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.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Williams
authors.affiliation: 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.
authors.forename: Jan-Åke
authors.initials: JÅ
authors.lastname: Gustafsson
authors.affiliation: 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.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Ström
mesh_terms: D015687:Cell Hypoxia / Q000235:genetics; D045744:Cell Line, Tumor; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055550:Protein Stability; D020218:Response Elements; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: C000600034:ESR2 protein, human; D047629:Estrogen Receptor beta; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1