Open AccessEstrogen Receptor Beta Displays Cell Cycle-Dependent Expression and Regulates the G1 Phase through a Non-Genomic Mechanism in Prostate Carcinoma Cells
Author(s) -
Antoni Hurtado,
Tomàs Pinós,
Anna Barbosa-Desongles,
Sandra López-Avilés,
Jordi Barquinero,
Jordi Pétriz,
Albert Santamaria-Martínez,
J. Morote,
Inés de Torres,
Joaquim Bellmunt,
Jaume Reventós,
Francina Munell
Publication year - 2008
Publication title -
analytical cellular pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.576
H-Index - 24
eISSN - 2210-7185
pISSN - 2210-7177
DOI - 10.1155/2008/129726
Subject(s) - transactivation , lncap , cyclin d1 , estrogen receptor , estrogen receptor beta , ap 1 transcription factor , estrogen receptor alpha , cell cycle , biology , cancer research , microbiology and biotechnology , chemistry , transcription factor , prostate cancer , cell , cancer , gene , genetics , breast cancer
Background : It is well known that estrogens regulate cell cycle progression, but the specific contributions and mechanisms of action of the estrogen receptor beta (ER β ) remain elusive. Methods : We have analyzed the levels of ER β 1 and ER β 2 throughout the cell cycle, as well as the mechanisms of action and the consequences of the over-expression of ER β 1 in the human prostate cancer LNCaP cell line. Results : Both ER β 1 mRNA and protein expression increased from the G1 to the S phase and decreased before entering the G2/M phase, whereas ER β 2 levels decreased during the S phase and increased in the G2/M phase. ER β 1 protein was detected in both the nuclear and non-nuclear fractions, and ER β 2 was found exclusively in the nucleus. Regarding the mechanisms of action, endogenous ER β was able to activate transcription via ERE during the S phase in a ligand-dependent manner, whereas no changes in AP1 and NF κ B transactivation were observed after exposure to estradiol or the specific inhibitor ICI 182,780. Over-expression of either wild type ER β 1 or ER β 1 mutated in the DNA-binding domain caused an arrest in early G1. This arrest was accompanied by the interaction of over-expressed ER β 1 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–ER β 1 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 ER β isoforms are differentially expressed during the cell cycle and that ER β regulates the G1 phase by a non-genomic mechanism.