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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Molecular and Cellular Endocrinology; v. 430, n. C, p. 12-24, JUL 15 2016.
• Citações Web of Science: 11

Resumo

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)

• Processo FAPESP: 08/56564-1 - Receptores estrogênicos: expressão, regulação, sinalização e função no sistema reprodutor masculino, mama e cérebro
• Beneficiário: Catarina Segreti Porto
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/05292-2 - Receptores estrogênicos e vias de sinalização intracelular envolvidas na regulação da proliferação de células do câncer testicular e do câncer prostático resistente à castração
• Beneficiário: Catarina Segreti Porto
• Modalidade de apoio: Auxílio à Pesquisa - Regular