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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Lombardi, Ana Paola G. [1] ; Pisolato, Raisa [1] ; Vicente, Carolina M. [1] ; Lazari, Maria Fatima M. [1] ; Lucas, Thais F. G. [1] ; Porto, Catarina S. [1]
Total Authors: 6
Affiliation:
[1] Univ Fed Sao Paulo, INFAR, Escola Paulista Med, Sect Expt Endocrinol, Dept Pharmacol, Rua Tres de Maio 100, BR-04044020 Sao Paulo, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Molecular and Cellular Endocrinology; v. 430, n. C, p. 12-24, JUL 15 2016.
Web of Science Citations: 11
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. (AU)

FAPESP's process: 08/56564-1 - Estrogen receptors: expression, regulation, signaling, and function in the male reproductive tract, breast, and brain
Grantee:Catarina Segreti Porto
Support type: Research Projects - Thematic Grants
FAPESP's process: 14/05292-2 - Estrogen receptors and intracellular signaling pathways involved in the regulation of cell proliferation of testicular cancer and castration-resistant prostate cancer
Grantee:Catarina Segreti Porto
Support type: Regular Research Grants