title: GPER functions as a tumor suppressor in triple-negative breast cancer cells.
abstract: BACKGROUND
  The orphan, membrane-bound estrogen receptor (GPER) is expressed at high levels in a large fraction of breast cancer patients and its expression is favorable for patients' survival.
  
  
  METHODS
  We investigated the role of GPER as a potential tumor suppressor in triple-negative breast cancer cells MDA-MB-231 and MDA-MB-468 using cell cycle analysis and apoptosis assay. The constitutive activity of GPER was investigated.
  
  
  RESULTS
  GPER-specific activation with G-1 agonist inhibited breast cancer cell growth in concentration-dependent manner via induction of the cell cycle arrest in G2/M phase, enhanced phosphorylation of histone H3 and caspase-3-mediated apoptosis. Analysis of the methylation status of the GPER promoter in the triple-negative breast cancer cells and in tissues derived from breast cancer patients revealed that GPER amount is regulated by epigenetic mechanisms and GPER expression is inactivated by promoter methylation. Furthermore, GPER expression was induced by stress factors, such as radiation, and GPER amount inversely correlated with the p53 expression level.
  
  
  CONCLUSIONS
  Overall, our results establish the protective role in breast cancer tumorigenesis, and the cell surface expression of GPER makes it an excellent potential therapeutic target for triple-negative breast cancer.
authors.affiliation: Department of Obstetrics and Gynecology, University of Magdeburg, Gerhart-Hauptmann Str 35, Magdeburg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Weißenborn
authors.forename: Tanja
authors.initials: T
authors.lastname: Ignatov
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Ochel
authors.forename: Serban Dan
authors.initials: SD
authors.lastname: Costa
authors.forename: Ana Claudia
authors.initials: AC
authors.lastname: Zenclussen
authors.forename: Zoya
authors.initials: Z
authors.lastname: Ignatova
authors.forename: Atanas
authors.initials: A
authors.lastname: Ignatov
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D063646:Carcinogenesis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003517:Cyclopentanes / Q000008:administration & dosage; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D011804:Quinolines / Q000008:administration & dosage; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics*; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C517943:1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone; D003517:Cyclopentanes; C109584:GPER1 protein, human; D011804:Quinolines; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D053148:Caspase 3