Cold-shock domain family member YB-1 expression in endometrium and endometriosis

Abstract

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.