RESUMO
BACKGROUND: The Y-box-binding protein (YB-1) is described as a potential oncogene highly expressed in tumors and associated with increased cell survival, proliferation, migration and anti-apoptotic signaling. The aim of our study was to examine the expression and role of YB-1 in human endometriosis (Eo) and its association with cell survival, proliferation and invasion. METHODS: We analyzed the gene and protein expression levels of YB-1 by quantitative real-time RT-PCR and immunoassays, respectively, in peritoneal macrophages, ovarian endometrioma and eutopic endometrial tissues/cells derived from women with (n= 120) and without (n= 91) Eo. We also evaluated the functional consequences of YB-1 knockdown in the Z12 Eo cell line by measuring cell proliferation [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid cell proliferation assay], invasion (Matrigel invasion assay) and spontaneous and tumour necrosis factor (TNFα)-induced RANTES (regulated upon activation, normal T-cell expressed and secreted chemokine) expression and apoptosis (ELISA-based assay). RESULTS: YB-1 gene and protein expression was statistically significantly higher in ovarian lesions, eutopic endometrium and peritoneal macrophages of patients with Eo in comparison with the control group. Interestingly, the strongest YB-1 expression was observed in the epithelial compartment of endometrial tissues. In the Z12 cell line, YB-1 knockdown resulted in significant cell growth inhibitory effects including reduced cell proliferation and increased rates of spontaneous and TNFα-induced apoptosis. Significantly, higher RANTES expression and decreased cell invasion in vitro were also associated with YB-1 inactivation. CONCLUSION: High YB-1 expression could have an impact on the development and progression of Eo. This study suggests the role of YB-1 as a potential therapeutic target for Eo patients.
Assuntos
Endometriose/metabolismo , Endométrio/metabolismo , Regulação da Expressão Gênica , Proteína 1 de Ligação a Y-Box/biossíntese , Adulto , Apoptose , Proliferação de Células , Sobrevivência Celular , Quimiocina CCL5/metabolismo , Colágeno/química , Combinação de Medicamentos , Feminino , Humanos , Inflamação , Laminina/química , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/metabolismo , Modelos Biológicos , Ovário/patologia , Proteoglicanas/química , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/metabolismoAssuntos
Sobrevivência de Enxerto/imunologia , Interleucina-2/imunologia , Transplante de Rim/imunologia , Proteínas Recombinantes de Fusão , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Formação de Anticorpos/efeitos dos fármacos , Basiliximab , Criança , Creatinina/sangue , Infecções por Citomegalovirus/epidemiologia , Daclizumabe , Quimioterapia Combinada , Rejeição de Enxerto/patologia , Humanos , Imunoglobulina G/uso terapêutico , Imunossupressores/uso terapêutico , Interleucina-2/biossíntese , Transplante de Rim/mortalidade , Complicações Pós-Operatórias/virologia , Taxa de Sobrevida , Resultado do TratamentoRESUMO
A 57 year-old-man with acute aortic dissection (DeBakey type I) who developed right coronary artery dissection without acute myocardial infarction. He was successful surgically treated and became asymptomatic.
