title: Estrogen receptor beta displays cell cycle-dependent expression and regulates the G1 phase through a non-genomic mechanism in prostate carcinoma cells.
abstract: BACKGROUND
  It is well known that estrogens regulate cell cycle progression, but the specific contributions and mechanisms of action of the estrogen receptor beta (ERbeta) remain elusive.
  
  
  METHODS
  We have analyzed the levels of ERbeta1 and ERbeta2 throughout the cell cycle, as well as the mechanisms of action and the consequences of the over-expression of ERbeta1 in the human prostate cancer LNCaP cell line.
  
  
  RESULTS
  Both ERbeta1 mRNA and protein expression increased from the G1 to the S phase and decreased before entering the G2/M phase, whereas ERbeta2 levels decreased during the S phase and increased in the G2/M phase. ERbeta1 protein was detected in both the nuclear and non-nuclear fractions, and ERbeta2 was found exclusively in the nucleus. Regarding the mechanisms of action, endogenous ERbeta was able to activate transcription via ERE during the S phase in a ligand-dependent manner, whereas no changes in AP1 and NFkappaB transactivation were observed after exposure to estradiol or the specific inhibitor ICI 182,780. Over-expression of either wild type ERbeta1 or ERbeta1 mutated in the DNA-binding domain caused an arrest in early G1. This arrest was accompanied by the interaction of over-expressed ERbeta1 with c-Jun N-terminal protein kinase 1 (JNK1) and a decrease in c-Jun phosphorylation and cyclin D1 expression. The administration of ICI impeded the JNK1-ERbeta1 interaction, increased c-Jun phosphorylation and cyclin D1 expression and allowed the cells to progress to late G1, where they became arrested.
  
  
  CONCLUSIONS
  Our results demonstrate that, in LNCaP prostate cancer cells, both ERbeta isoforms are differentially expressed during the cell cycle and that ERbeta regulates the G1 phase by a non-genomic mechanism.
authors.affiliation: Unitat de Recerca Biomèdica, Institut de Recerca, Hospital Universitari Vall d'Hebrón, 8035 Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Hurtado
authors.forename: Tomàs
authors.initials: T
authors.lastname: Pinós
authors.forename: Anna
authors.initials: A
authors.lastname: Barbosa-Desongles
authors.forename: Sandra
authors.initials: S
authors.lastname: López-Avilés
authors.forename: Jordi
authors.initials: J
authors.lastname: Barquinero
authors.forename: Jordi
authors.initials: J
authors.lastname: Petriz
authors.forename: Albert
authors.initials: A
authors.lastname: Santamaria-Martínez
authors.forename: Joan
authors.initials: J
authors.lastname: Morote
authors.forename: Inés
authors.initials: I
authors.lastname: de Torres
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
authors.forename: Jaume
authors.initials: J
authors.lastname: Reventós
authors.forename: Francina
authors.initials: F
authors.lastname: Munell
mesh_terms: D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000077267:Fulvestrant; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000235:genetics; D011471:Prostatic Neoplasms / Q000473:pathology*; D011485:Protein Binding / Q000187:drug effects; D016196:S Phase / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics; D019076:Transgenes / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D004965:Estrogen Antagonists; D047629:Estrogen Receptor beta; D050505:Mutant Proteins; D000077267:Fulvestrant; D004958:Estradiol