12-HETE (stereoisomer not defined) is the dominant arachidonic acid metabolite in cultured PC3 human prostate cancer cells and its levels in human prostate cancer tissue exceed by >9-fold its levels in normal human prostate tissue.  Furthermore, 12(S)-HETE a) increases the expression of Alpha-v beta-5 cell surface adhesion molecule and associated with this the survival of cultured PC3 cells; b) promotes the phosphorylation of retinoblastoma protein to inhibit its tumor suppressor function while promoting the proliferation of cultured PC3 cells; c) stimulates PC3 cells to activate the Mitogen-activated protein kinase kinase/extracellular signal-regulated kinases-1/2 pathway and the NFκB pathways that lead to cell proliferation; d) reverses the apoptosis-inducing (i.e. cell-killing) effect of pharmacologically inhibiting 12-LO in cultured DU145 human prostate cancer cells; e) promotes the induction of cyclooxygenase-1 and thereby the synthesis of this enzyme's growth-promoting arachidonic acid metabolite, PGE2, in cultured PC3 and LNCaP human prostate cancer cells; and f) induces cultured PC3 cells to express Vascular endothelial growth factor (VEGF), a protein that stimulates the formation of the microvasculature which assists in the metastasis of cancer.  These results suggest that the 12(S)-HETE made by prostate cancer tissues serves to promote the growth and spread of this cancer.  Since it mediates the action of 12(S)-HETE in stimulating cultured PC3 cells to activate the Mitogen-activated protein kinase kinase/Extracellular signal-regulated kinases-1/2 pathway and NFκB pathways, the GPR31 receptor may contribute to the pro-malignant activity of 12(S)-HETE.  However, LNCaP and PC3 cells also express BLT2 receptors; in LNCaP cells, BLT2 receptors are positively linked (i.e. stimulate the expression of) to the growth- and metastasis-promoting androgen receptor; in PC3 cells, BLT2 receptors stimulate the NF-κB pathway to inhibit the apoptosis caused by cell detachment from surfaces (i.e. Anoikis; and, in BLT2-overexpressing PWR-1E non-malignant prostate cells, 12(S)-HETE diminish anoikis-induced apoptosis. Thus, the role of 12(S)-HETE in human prostate cancer, if any, may involve its activation of one or both of the GPR31 and BLT2 receptors.