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Mol Cell Endocrinol ; 483: 11-23, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30660702

RESUMO

The aim of the present study was to investigate the subcellular localization of estrogen receptors ERα and ERß in androgen-independent prostate cancer cell line DU-145, and the possible role of exportin CRM1 on ERs distribution. In addition, we evaluated the ERs contribution to activation of ERK1/2 and AKT. Immunostaining of ERα and ERß was predominantly found in the extranuclear regions of DU-145 cells. CRM1 inhibitor Leptomycin B reduced drastically the presence of ERα and ERß in the extranuclear regions and increased in the nuclei, indicating the possible involvement of CRM1 on ERs nuclear-cytoplasmic shuttling. 17ß-estradiol (E2), ERα-selective agonist PPT and ERß-selective agonist DPN induced a rapid increase on ERK1/2 phosphorylation. E2-induced ERK1/2 activation was partially inhibited when cells were pretreated with ERα- or ERß-selective antagonists, and blocked by simultaneous pretreatment with both antagonists, suggesting ERα/ß heterodimers formation. Furthermore, E2 treatment did not activate AKT pathway. Therefore, we highlighted a possible crosstalk between extranuclear and nuclear ERs and their upstream and downstream signaling molecules as an important mechanism to control ER function as a potential therapeutic target in prostate cancer cells.


Assuntos
Citoplasma/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Carioferinas/metabolismo , Neoplasias da Próstata/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Estradiol/farmacologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Fosforilação/efeitos dos fármacos , Transporte Proteico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína Exportina 1
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