Modulating effects of PTEN in the loop of autocrine VEGF-A/VEGFR-2 in hemangioma-derived cells

Abstract

Objective To explore the expression of PTEN in infantile hemangioma (IH) and determine its involvement in the regulation of VEGF-A/VEGFR-2 loop of hemangioma-derived endothelial cells (HemECs). Methods Real-time polymerase chain reaction (PCR) was performed for evaluating the expression of PTEN in proliferating IH tissues and normal skin. Protein expressions of PTEN in HemECs and normal endothelial cells (ECs) were assayed by Western blot. And the effects of PTEN were also analyzed in regulating HemEC proliferation and apoptosis. Results The expression of tumor suppressor PTEN decreased in proliferating IH tissues as compared with normal skin. As compared with normal' endothelial cells (HUVECs), HemECs showed a down-regulation of PTEN protein (0.08±0.02 vs 1.86±0.41). The expression of endogenous VEGF and activation of VEGFR-2 decreased markedly in PTEN-transfected HemECs as compared with control cells (1.27±0.25 vs 0.09±0.03). In contrast, there was no significant effect of PTEN on VEGFR-2 expression (2.32±0.51 vs 2.35±0.42). An up-regulation of PTEN decreased HemEC proliferation and caused heightened sensitivity to apoptosis in HemEcs. Conclusions PTEN prevents the activation of VEGF-A/VEGFR-2 loop in HemECs. Also it is capable of inhibiting HemECs proliferation and inducing HemECs apoptosis in vitro. Key words: Hemangioma; Endothelial cell; Vascular endothelial growth factor