RESUMO
The aim of the present study was to investigate the role of estrogen receptor (ER)α and ERß, and galectin3 (GAL3) in migration and invasion of androgenindependent DU145 prostate cancer cells, and to examine the regulation of the expression of GAL3 by the activation of these receptors. Wound healing and cell invasion assays were performed using the control (basal level of cellular function) and treated DU145 cells. At 24 h of treatment, 17ßestradiol (E2), the ERαselective agonist, 4,4',4"(4propyl(1H)pyrazole1,3,5triyl)trisphenol (PPT), or the ERßselective agonist, 2,3bis(4hydroxyphenyl)propionitrile (diarylprepionitrile; DPN), increased the migration and invasion of the DU145 cells. Pretreatment with the ERα and ERßselective antagonists blocked these effects, indicating that ERα and ERß are upstream receptors regulating these processes. Western blot analysis and immunofluorescence staining for the detection of the GAL3 were performed using the control and treated DU145 cells. Treatment of the DU145 cells with E2, PPT or DPN for 24 h increased the expression of the GAL3 compared to the control. Furthermore, a specific inhibitor of GAL3 (VA03) inhibited the migration and invasion of DU145 cells, indicating the involvement of the complex ERα/GAL3 and ERß/GAL3 in the regulation of these processes. On the whole, the present study demonstrates that the activation of both ERs increases the expression and signaling of GAL3, and promotes the migration and invasion of DU145 cells. The findings of the present study provide novel insight into the signatures and molecular mechanisms of ERα and ERß in DU145 cells.
Assuntos
Neoplasias da Próstata , Receptores de Estrogênio , Masculino , Humanos , Receptor alfa de Estrogênio/metabolismo , Galectina 3 , Androgênios , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Estradiol/farmacologiaRESUMO
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.