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

The aim of the present study was to investigate the subcellular localization of estrogen receptors ER alpha and ER beta 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 ER alpha and ER beta was predominantly found in the extranuclear regions of DU-145 cells. CRM1 inhibitor Leptomycin B reduced drastically the presence of ER alpha and ER beta in the extranuclear regions and increased in the nuclei, indicating the possible involvement of CRM1 on ERs nuclear-cytoplasmic shuffling. 17 beta-estradiol (E2), ER alpha-selective agonist PPT and ER beta-selective agonist DPN induced a rapid increase on ERK1/2 phosphorylation. E2-induced ERK1/2 activation was partially inhibited when cells were pretreated with ER alpha- or ER beta-selective antagonists, and blocked by simultaneous pretreatment with both antagonists, suggesting ER alpha/beta 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.