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.
Urology Research Center, Medical University of Ohio at Toledo, Toledo, Ohio OH 43699-0008, USA.
N Patrick
NP
McCabe
Steven H
SH
Selman
Jerzy
J
Jankun
D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D001792:Blood Platelets / Q000201:enzymology; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009389:Neovascularization, Pathologic; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D042461:Vascular Endothelial Growth Factor A; D001092:Arachidonate 12-Lipoxygenase