Estrogen receptor beta (ER beta) mediates expression of beta-catenin and proliferation in prostate cancer cell line PC-3

Estrogen receptor beta (ER beta) mediates expression of beta-catenin and proliferation in prostate cancer cell line PC-3

Author Lombardi, Ana Paola G. Autor UNIFESP Google Scholar
Pisolato, Raisa Autor UNIFESP Google Scholar
Vicente, Carolina M. Autor UNIFESP Google Scholar
Lazari, Maria Fatima M. Autor UNIFESP Google Scholar
Lucas, Thais F. G. Autor UNIFESP Google Scholar
Porto, Catarina S. Autor UNIFESP Google Scholar
Abstract The aim of the present study was to characterize the mechanism underlying estrogen effects on the androgen-independent prostate cancer cell line PC-3. 17 beta-estradiol and the ER beta-selective agonist DPN, but not the ER alpha-selective agonist PPT, increased the incorporation of [methyl-H-3]thymidine and the expression of Cyclin D2, suggesting that ER beta mediates the proliferative effect of estrogen on PC-3 cells. In addition, upregulation of Cyclin D2 and incorporation of [methyl-H-3]thymidine induced by 17 beta-estradiol and DPN were blocked by the ER beta-selective antagonist PHTPP in PC-3 cells. Upregulation of Cyclin D2 and incorporation of [methyl-H-3]thymidine induced by DPN were also blocked by PKF118-310, a compound that disrupts beta-catenin-TCF (T-cell-specific transcription factor) complex, suggesting the involvement of beta-catenin in the estradiol effects in PC-3 cells. A diffuse immunostaining for non-phosphorylated beta-catenin was detected in the cytoplasm of PC-3 cells. Low levels of nonphosphorylated beta-catenin immunostaining were also detected near the plasma membrane and in nuclei. Treatment of PC-3 cells with 17 beta-estradiol or DPN markedly increased non-phosphorylated beta-catenin expression. These effects were blocked by pretreatment with the ER beta-selective antagonist PHTPP, PI3K inhibitor Wortmannin or AKT inhibitor MK-2206, indicating that ER beta-PI3K/AKT mediates non-phosphorylated beta-catenin expression. Cycloheximide blocked the DPN-induced upregulation of nonphosphorylated beta-catenin, suggesting de novo synthesis of this protein. In conclusion, these results suggest that estrogen may play a role in androgen-independent prostate cancer cell proliferation through a novel pathway, involving ER beta-mediated activation of beta-catenin. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
Keywords ER beta
beta-catenin
Cyclin D2
Prostate cancer cells
xmlui.dri2xhtml.METS-1.0.item-coverage Clare
Language English
Sponsor Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
Grant number FAPESP: 2008/56564-1
FAPESP: 2014/05292-2
Date 2016
Published in Molecular And Cellular Endocrinology. Clare, v. 430, p. 12-24, 2016.
ISSN 0303-7207 (Sherpa/Romeo, impact factor)
Publisher Elsevier Ireland Ltd
Extent 12-24
Origin http://dx.doi.org/10.1016/j.mce.2016.04.012
Access rights Closed access
Type Article
Web of Science ID WOS:000378457200002
URI https://repositorio.unifesp.br/handle/11600/57539

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