Estrogen receptors localization and signaling pathways in DU-145 human prostate cancer cells. (1st March 2019)

• Record Type: Journal Article
• 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.
• Is Part Of: Molecular and cellular endocrinology. Volume 483(2019)
• Page Start: 11
• Page End: 23
• Publication Date: 2019-03-01
• Subjects: ERα -- ERβ -- CRM1 -- ERK1/2 -- AKT -- Prostate cancer cell; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2018.12.015
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: 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. Highlights: 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.