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

• Published in: Molecular and cellular endocrinology 2019-03, Vol.483, p.11-23
• Main Authors: Souza, Deborah S., Lombardi, Ana Paola G., Vicente, Carolina M., Lucas, Thaís Fabiana G., Erustes, Adolfo G., Pereira, Gustavo J.S., Porto, Catarina S.
• Format: Article
• Language: English
• Subjects: AKT; Cell Line, Tumor; Cell Nucleus - metabolism; CRM1; Cytoplasm - metabolism; ERK1/2; ERα; ERβ; Estradiol - pharmacology; Estrogen Receptor alpha - metabolism; Estrogen Receptor beta - metabolism; Exportin 1 Protein; Humans; Karyopherins - metabolism; Male; MAP Kinase Signaling System - drug effects; Phosphorylation - drug effects; Prostate cancer cell; Prostatic Neoplasms - metabolism; Protein Transport; Proto-Oncogene Proteins c-akt - metabolism; Receptors, Cytoplasmic and Nuclear - metabolism
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2018.12.015

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. •ERα and ERβ are mainly present in the extranuclear regions of DU-145 cells.•CRM1 is involved in the nuclear-cytoplasmic shuttling of ERs.•ERα/β heterodimers induces ERK1/2 phosphorylation.•These mechanisms may be involved in development of prostate cancer and resistance to therapy.