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Cellular Oncology
Volume 30 (2008), Issue 4, Pages 349-365

Estrogen Receptor Beta Displays Cell Cycle-Dependent Expression and Regulates the G1 Phase through a Non-Genomic Mechanism in Prostate Carcinoma Cells

Antoni Hurtado,1 Tomàs Pinós,1 Anna Barbosa-Desongles,1 Sandra López-Avilés,2 Jordi Barquinero,3 Jordi Petriz,1 Albert Santamaria-Martínez,1 Joan Morote,4 Inés de Torres,5 Joaquim Bellmunt,6 Jaume Reventós,1 and Francina Munell1

1Unitat de Recerca Biomèdica, Institut de Recerca, Hospital Universitari Vall d’Hebrón, 8035 Barcelona, Spain
2Departatment de Biologia Cellular i Anatomia Patológica, Facultat de Medicina, Universitat de Barcelona, Hospital Clínic, 08036 Barcelona, Spain
3Unitat de Diagnostic i Terapia Molecular, Banc de Sang i Teixits, 08035 Barcelona, Spain
4Servei d'Urologia, Hospital Universitari Vall d’Hebrón, 08035 Barcelona, Spain
5Servei d'Anatomia Patológica, Hospital Universitari Vall d’Hebrón, 08035 Barcelona, Spain
6Servei d'Oncologia, Hospital Universitari Vall d’Hebrón, 08035 Barcelona, Spain

Copyright © 2008 Hindawi Publishing Corporation and the authors. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.