title: Agonists and knockdown of estrogen receptor β differentially affect invasion of triple-negative breast cancer cells in vitro.
abstract: Estrogen receptor β (ERβ) is expressed in the majority of invasive breast cancer cases, irrespective of their subtype, including triple-negative breast cancer (TNBC). Thus, ERβ might be a potential target for therapy of this challenging cancer type. In this in vitro study, we examined the role of ERβ in invasion of two triple-negative breast cancer cell lines.
  
  
  
  MDA-MB-231 and HS578T breast cancer cells were treated with the specific ERβ agonists ERB-041, WAY200070, Liquiritigenin and 3β-Adiol. Knockdown of ERβ expression was performed by means of siRNA transfection. Effects on cellular invasion were assessed in vitro by means of a modified Boyden chamber assay. Transcriptome analyses were performed using Affymetrix Human Gene 1.0 ST microarrays. Pathway and gene network analyses were performed by means of Genomatix and Ingenuity Pathway Analysis software.
  
  
  
  Invasiveness of MBA-MB-231 and HS578T breast cancer cells decreased after treatment with ERβ agonists ERB-041 and WAY200070. Agonists Liquiritigenin and 3β-Adiol only reduced invasion of MDA-MB-231 cells. Knockdown of ERβ expression increased invasiveness of MDA-MB-231 cells about 3-fold. Transcriptome and pathway analyses revealed that ERβ knockdown led to activation of TGFβ signalling and induced expression of a network of genes with functions in extracellular matrix, tumor cell invasion and vitamin D3 metabolism.
  
  
  
  Our data suggest that ERβ suppresses invasiveness of triple-negative breast cancer cells in vitro. Whether ERβ agonists might be useful drugs in the treatment of triple-negative breast cancer, has to be evaluated in further animal and clinical studies.
authors.affiliation: Department of Gynaecology and Obstetrics, University Medical Center Regensburg, Caritas-Hospital St. Josef, Landshuter Str. 65, 93053, Regensburg, Germany. sschueler@caritasstjosef.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schüler-Toprak
authors.affiliation: Department of Gynaecology and Obstetrics, University Medical Center Regensburg, Caritas-Hospital St. Josef, Landshuter Str. 65, 93053, Regensburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Häring
authors.affiliation: Department of Gynaecology and Obstetrics, University Medical Center Regensburg, Caritas-Hospital St. Josef, Landshuter Str. 65, 93053, Regensburg, Germany.
authors.forename: Elisabeth C
authors.initials: EC
authors.lastname: Inwald
authors.affiliation: Center of Excellence for Fluorescent Bioanalytics (KFB), Am BioPark 9, 93053, Regensburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Moehle
authors.affiliation: Department of Gynaecology and Obstetrics, University Medical Center Regensburg, Caritas-Hospital St. Josef, Landshuter Str. 65, 93053, Regensburg, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Ortmann
authors.affiliation: Department of Gynaecology and Obstetrics, University Medical Center Regensburg, Caritas-Hospital St. Josef, Landshuter Str. 65, 93053, Regensburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Treeck
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000037:antagonists & inhibitors*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D053263:Gene Regulatory Networks; D006801:Humans; D066298:In Vitro Techniques; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome / Q000187:drug effects; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D047629:Estrogen Receptor beta; D004967:Estrogens; D012333:RNA, Messenger; D034741:RNA, Small Interfering
keywords: Cell culture; Estrogen receptor beta; Invasion; Triple-negative breast cancer