title: Prospects of estrogen receptor β activation in the treatment of castration-resistant prostate cancer.
abstract: Advanced prostate cancer can develop into castration-resistant prostate cancer (CRPC). This process is mediated either by intratumoral ligand synthesis or by mutations or aberrations of the androgen receptor (AR) or its cofactors. To date, no curative therapy for CRPC is available, as AR-targeted therapies eventually result in the development of resistance. The human prostate cancer cell line VCaP (vertebral cancer of the prostate) overexpresses AR and its splice variants (ARVs) as a mechanism of resistance to androgen-deprivation therapy (ADT) of external and intratumoral origin. In the present study, we demonstrate that stimulating estrogen receptor β activity with the specific agonist 8β-VE2 in VCaP cells in successive stages of ADT induced a time- and dose-dependent decrease in cell survival and an increase in apoptosis. Furthermore, 8β-VE2 treatment reduced the overexpression of the AR as well as ARVs in VCaP cells under maximum ADT. Our results indicate that decreased survival of the androgen-dependent CRPC cells employing apoptosis together with the regulative effect on AR expression could have beneficial effects over current AR-targeting therapies.
authors.affiliation: Institute of Human Genetics, University Medical Center Goettingen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Gehrig
authors.affiliation: Institute of Human Genetics, University Medical Center Goettingen, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Kaulfuß
authors.affiliation: Department of Experimental Endocrinology, University Medical Center Goettingen, Germany.
authors.forename: Hubertus
authors.initials: H
authors.lastname: Jarry
authors.affiliation: Institute of Pathology, University Medical Center Goettingen, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Bremmer
authors.affiliation: Department of Neurology, University of Essen, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Stettner
authors.affiliation: Institute of Human Genetics, University Medical Center Goettingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Burfeind
authors.affiliation: Department of Urology, University Medical Center Goettingen, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Thelen
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D047629:Estrogen Receptor beta / Q000819:agonists*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation; D014753:Vinyl Compounds / Q000494:pharmacology*
chemical_list: C410798:AR protein, human; C000600034:ESR2 protein, human; D047629:Estrogen Receptor beta; D011944:Receptors, Androgen; D014753:Vinyl Compounds
keywords: 8β-VE2; ADT; androgen receptor; estrogen receptor β; therapy resistance