Vascular endothelial growth factor production in human prostate cancer cells is stimulated by overexpression of platelet 12-lipoxygenase

BACKGROUND Elevated platelet 12‐Lipoxygenase (P12‐LOX) expression is associated with advanced stage and grade prostate cancer and overexpression in PC‐3 cells promotes tumor growth and angiogenesis. The mechanisms underlying the role of P12‐LOX in angiogenesis remain unclear. METHODS Enzyme linked immunosorbent assays were used to measure 12(S)‐hydroxyeicosatetraenoic acid (12(S)‐HETE) and vascular endothelial growth factor (VEGF) in conditioned media of PC‐3 cells stably overexpressing human P12‐LOX. Immunoblotting was used to observe stimulation of signal transduction in prostate cancer cell lines following exposure to 12(S)‐HETE. RESULTS P12‐LOX overexpression promotes increased accumulation of 12(S)‐HETE and VEGF in culture media leading to constitutive ERK1/2 phosphorylation. 12(S)‐HETE stimulates ERK1/2 phosphorylation via a pertussis toxin sensitive G‐protein coupled receptor (GPCR) and MEK; the inhibition of which reduces VEGF accumulation by 36% and 70%, respectively. CONCLUSIONS Our data provide insight into a possible mechanism by which prostate cancer cells with elevated expression of P12‐LOX stimulate VEGF production, thus increasing their angiogenic potential. Prostate © 2006 Wiley‐Liss, Inc.