Phosphatase of regenerating liver-3 induces angiogenesis by increasing extracellular signal-regulated kinase phosphorylation in endometrial adenocarcinoma.

Objective:The aim of this study was to investigate the mechanism by which phosphatase of regenerating liver-3 (PRL-3) induces angiogenesis in endometrial adenocarcinoma tissues and cells. Methods: We investigated the expression of PRL-3 and vascular endothelial growth factor (VEGF) in samples from 124 patients with endometrial adenocarcinoma using immunohistochemical staining. The relationship between PRL-3 expression and microvessel density (MVD), clinicopathological factors and surgical treatment outcome was also studied. Following this, we studied the effect on cell lines of blocking or upregulating PRL-3. Results: PRL-3 expression in endometrial adenocarcinonna was high, and this overexpression is correlated with advanced clinical stage (p = 0.008), lymph node metastasis (p = 0.016) and poor postoperative survival. PRL-3 overexpression was associated with VEGF (p = 0.001) expression and MVD (p = 0.005). Upregulating PRL-3 expression promoted VEGF and phosphorylated extracellular signal-regulated kinase (pERK) expression. Blocking PRL-3 expression inhibited VEGF and pERK expression. Following inhibition of pERK, VEGF expression was downregulated. Conclusions: PRL-3 induces microvascular vessel formation by facilitating VEGF expression in endometrial adenocarcinoma tissues. PRL-3 upregulates pERK expression and activity, facilitating VEGF expression and accelerating angiogenesis. Copyright (C) 2013 S. Karger AG, Basel