Estrogen receptor beta displays cell cycle-dependent expression and regulates the G1 phase through a non-genomic mechanism in prostate carcinoma cells

Background: It is well known that estrogens regulate cell cycle progression, but the specific contributions and mechanisms of action of the estrogen receptor beta (ERβ) remain elusive. Methods: We have analyzed the levels of ERβ1 and ERβ2 throughout the cell cycle, as well as the mechanisms of actio...

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Autores: Hurtado, Antoni, Pinós, Tomàs, Barbosa-Desongles, Anna, López-Avilés, Sandra, Barquinero, Jordi, Petriz, Jordi, Santamaria-Martínez, Albert, Morote, Joan, de Torres, Inés, Bellmunt, Joaquim, Reventós, Jaume, Munell, Francina
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2008
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/414660
Acceso en línea:http://hdl.handle.net/10261/414660
https://api.elsevier.com/content/abstract/scopus_id/47749124288
Access Level:acceso abierto
Palabra clave:AP1
Cell cycle
ERβ1
ERβ2
ERE
ICI 182,780
LNCaP
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repository_id_str
spelling Estrogen receptor beta displays cell cycle-dependent expression and regulates the G1 phase through a non-genomic mechanism in prostate carcinoma cellsHurtado, AntoniPinós, TomàsBarbosa-Desongles, AnnaLópez-Avilés, SandraBarquinero, JordiPetriz, JordiSantamaria-Martínez, AlbertMorote, Joande Torres, InésBellmunt, JoaquimReventós, JaumeMunell, FrancinaAP1Cell cycleERβ1ERβ2EREICI 182,780LNCaPBackground: It is well known that estrogens regulate cell cycle progression, but the specific contributions and mechanisms of action of the estrogen receptor beta (ERβ) remain elusive. Methods: We have analyzed the levels of ERβ1 and ERβ2 throughout the cell cycle, as well as the mechanisms of action and the consequences of the over-expression of ERβ1 in the human prostate cancer LNCaP cell line. Results: Both ERβ1 mRNA and protein expression increased from the G1 to the S phase and decreased before entering the G2/M phase, whereas ERβ2 levels decreased during the S phase and increased in the G2/M phase. ERβ1 protein was detected in both the nuclear and non-nuclear fractions, and ERβ2 was found exclusively in the nucleus. Regarding the mechanisms of action, endogenous ERβ was able to activate transcription via ERE during the S phase in a ligand-dependent manner, whereas no changes in AP1 and NFκB transactivation were observed after exposure to estradiol or the specific inhibitor ICI 182,780. Over-expression of either wild type ERβ1 or ERβ1 mutated in the DNA-binding domain caused an arrest in early G1. This arrest was accompanied by the interaction of over-expressed ERβ1 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–ERβ1 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 ERβ isoforms are differentially expressed during the cell cycle and that ERβ regulates the G1 phase by a non-genomic mechanism.This work was supported by grants from the Ministerio de Educación y Ciencia (PM 1999-0134), theMinisterio de Sanidad y Consumo (PI020772) and theFundación para la Investigación en Urología. The au-thors would like to thank Alex Bote (UCTS, Hospi-tal Vall d’Hebrón, Barcelona, Spain), Jaume Comas(Serveis Cientifico-Tècnics, Universitat de Barcelona,Barcelona, Spain), and Antoni Iborra (IBB, Universi-tat Autònoma de Barcelona, Bellaterra, Spain) for theirtechnical assistance, Rosa Aligué and Miguel Abal forher technical and scientific support, as well as Lisa Pic-cione, Alfons Macaya and Jason S. Carroll for correc-tion of the manuscriptPeer reviewedJohn Wiley & SonsIOS PressMinisterio de Educación y Ciencia (España)Ministerio de Sanidad y Consumo (España)Fundación Para la Investigación en Urología202620262008info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/414660https://api.elsevier.com/content/abstract/scopus_id/47749124288reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.3233/CLO-2008-0430Digital Object Identifier (DOI)Noinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4146602026-05-22T06:33:51Z
dc.title.none.fl_str_mv Estrogen receptor beta displays cell cycle-dependent expression and regulates the G1 phase through a non-genomic mechanism in prostate carcinoma cells
title Estrogen receptor beta displays cell cycle-dependent expression and regulates the G1 phase through a non-genomic mechanism in prostate carcinoma cells
spellingShingle Estrogen receptor beta displays cell cycle-dependent expression and regulates the G1 phase through a non-genomic mechanism in prostate carcinoma cells
Hurtado, Antoni
AP1
Cell cycle
ERβ1
ERβ2
ERE
ICI 182,780
LNCaP
title_short Estrogen receptor beta displays cell cycle-dependent expression and regulates the G1 phase through a non-genomic mechanism in prostate carcinoma cells
title_full Estrogen receptor beta displays cell cycle-dependent expression and regulates the G1 phase through a non-genomic mechanism in prostate carcinoma cells
title_fullStr Estrogen receptor beta displays cell cycle-dependent expression and regulates the G1 phase through a non-genomic mechanism in prostate carcinoma cells
title_full_unstemmed Estrogen receptor beta displays cell cycle-dependent expression and regulates the G1 phase through a non-genomic mechanism in prostate carcinoma cells
title_sort Estrogen receptor beta displays cell cycle-dependent expression and regulates the G1 phase through a non-genomic mechanism in prostate carcinoma cells
dc.creator.none.fl_str_mv Hurtado, Antoni
Pinós, Tomàs
Barbosa-Desongles, Anna
López-Avilés, Sandra
Barquinero, Jordi
Petriz, Jordi
Santamaria-Martínez, Albert
Morote, Joan
de Torres, Inés
Bellmunt, Joaquim
Reventós, Jaume
Munell, Francina
author Hurtado, Antoni
author_facet Hurtado, Antoni
Pinós, Tomàs
Barbosa-Desongles, Anna
López-Avilés, Sandra
Barquinero, Jordi
Petriz, Jordi
Santamaria-Martínez, Albert
Morote, Joan
de Torres, Inés
Bellmunt, Joaquim
Reventós, Jaume
Munell, Francina
author_role author
author2 Pinós, Tomàs
Barbosa-Desongles, Anna
López-Avilés, Sandra
Barquinero, Jordi
Petriz, Jordi
Santamaria-Martínez, Albert
Morote, Joan
de Torres, Inés
Bellmunt, Joaquim
Reventós, Jaume
Munell, Francina
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Educación y Ciencia (España)
Ministerio de Sanidad y Consumo (España)
Fundación Para la Investigación en Urología
dc.subject.none.fl_str_mv AP1
Cell cycle
ERβ1
ERβ2
ERE
ICI 182,780
LNCaP
topic AP1
Cell cycle
ERβ1
ERβ2
ERE
ICI 182,780
LNCaP
description Background: It is well known that estrogens regulate cell cycle progression, but the specific contributions and mechanisms of action of the estrogen receptor beta (ERβ) remain elusive. Methods: We have analyzed the levels of ERβ1 and ERβ2 throughout the cell cycle, as well as the mechanisms of action and the consequences of the over-expression of ERβ1 in the human prostate cancer LNCaP cell line. Results: Both ERβ1 mRNA and protein expression increased from the G1 to the S phase and decreased before entering the G2/M phase, whereas ERβ2 levels decreased during the S phase and increased in the G2/M phase. ERβ1 protein was detected in both the nuclear and non-nuclear fractions, and ERβ2 was found exclusively in the nucleus. Regarding the mechanisms of action, endogenous ERβ was able to activate transcription via ERE during the S phase in a ligand-dependent manner, whereas no changes in AP1 and NFκB transactivation were observed after exposure to estradiol or the specific inhibitor ICI 182,780. Over-expression of either wild type ERβ1 or ERβ1 mutated in the DNA-binding domain caused an arrest in early G1. This arrest was accompanied by the interaction of over-expressed ERβ1 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–ERβ1 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 ERβ isoforms are differentially expressed during the cell cycle and that ERβ regulates the G1 phase by a non-genomic mechanism.
publishDate 2008
dc.date.none.fl_str_mv 2008
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/414660
https://api.elsevier.com/content/abstract/scopus_id/47749124288
url http://hdl.handle.net/10261/414660
https://api.elsevier.com/content/abstract/scopus_id/47749124288
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.3233/CLO-2008-0430Digital Object Identifier (DOI)
No
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv John Wiley & Sons
IOS Press
publisher.none.fl_str_mv John Wiley & Sons
IOS Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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