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Estrogen receptors localization and signaling pathways in DU-145 human prostate cancer cells

2019; Elsevier BV; Volume: 483; Linguagem: Inglês

10.1016/j.mce.2018.12.015

1872-8057

Deborah Simão Souza, Ana Paola G. Lombardi, Carolina Meloni Vicente, Thaís F.G. Lucas, Adolfo Garcia Erustes, Gustavo J.S. Pereira, Catarina S. Porto,

Protein Kinase Regulation and GTPase Signaling

The aim of the present study was to investigate the subcellular localization of estrogen receptors ERα and ERβ 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 ERβ was predominantly found in the extranuclear regions of DU-145 cells. CRM1 inhibitor Leptomycin B reduced drastically the presence of ERα and ERβ in the extranuclear regions and increased in the nuclei, indicating the possible involvement of CRM1 on ERs nuclear-cytoplasmic shuttling. 17β-estradiol (E2), ERα-selective agonist PPT and ERβ-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 ERβ-selective antagonists, and blocked by simultaneous pretreatment with both antagonists, suggesting ERα/β 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.