| Full text | |
| 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 |