ABSTRACT
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-145â¯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.
