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Abstract

Arachidonic acid (AA) is the precursor for prostaglandin E 2 (PGE 2 ) synthesis and increases growth of prostate cancer cells. To further elucidate the mechanisms involved in AA-induced prostate cell growth, induction of c-fos expression by AA was investigated in a human prostate cancer cell line, PC-3. c-fos mRNA was induced shortly after addition of AA, along with a remarkable increase in PGE 2 production. c-fos expression and PGE 2 production induced by AA was blocked by a cyclo-oxygenase inhibitor, flurbiprofen, suggesting that PGE 2 mediated c-fos induction. Protein kinase A (PKA) inhibitor H-89 abolished induction of c-fos expression by AA, and partially inhibited PGE 2 production. Protein kinase C (PKC) inhibitor GF109203X had no significant effect on c-fos expression or PGE 2 production. Expression of prostaglandin (EP) receptors, which mediate signal transduction from PGE 2 to the cells, was examined by reverse transcription polymerase chain reaction in several human prostate cell lines. EP4 and EP2, which are coupled to the PKA signalling pathway, were expressed in all cells tested. Expression of EP1, which activates the PKC pathway, was not detected. The current study showed that induction of the immediate early gene c-fos by AA is mediated by PGE 2 , which activates the PKA pathway via the EP2/4 receptor in the PC-3 cells. © 2000 Cancer Research Campaign

Polyunsaturated fatty acid metabolism in prostate cancer

“…In mouse prostate cells, expression of Ep1 , Ep2 , and Ep4 is detectable (Chen et al, unpublished). Only EP2 and EP4 were detected in PC3, DU145, and LNCaP human prostate tumor cells, which is consistent with the literature [131, 132]. Aberrant TXA 2 signaling and TP expression is associated with prostate cancer, where a direct correlation was observed with tumor Gleason score and pathological state [133, 134].…”

Comparative Transcriptome Analysis Reveals Early Pregnancy-Specific Genes Expressed in Peripheral Blood of Pregnant Sows

“…The only one significantly enriched pathway, Arachidonic acid metabolism (containing differently expressed gene CBR1, CBR2 and GPX6 ), may be involved in early pregnancy by altering production of prostaglandins. The deduction is based on the following facts: First, arachidonic acid is the precursor molecule for prostaglandin E2 (PGE 2 ) synthesis [29] ; then CBR1 (carbonyl reductase 1, also referred to PG 9-ketoreductase) can convert PGE 2 into PGF 2α [24] , these two prostaglandins have pleiotropic effects during sow pregnancy, potentially involving in embryo development, ovarian function and maternal recognition of pregnancy [30] . Second, although the exact function of CBR2 in pig is not clear yet.…”

Roles of eicosanoids in prostate cancer

“…PGE 2 stimulates growth and invasion of prostate cancer cells through multiple signaling pathways. For examples, PGE 2 activates protein kinase A (PKA) pathway to induce the expression of c-fos mRNA and growth in PC-3 cells [55]. PGE 2 increases the secretion of vascular endothelial growth factor (VEGF) and cyclic adenosine monophosphate (cAMP) in PC-3 cells but less in DU-145 and LNCaP cells [56].…”

“…These findings suggest that EP receptors, particularly EP 1 receptor, may have an important role in prostate cancer progression. Interestingly, EP 2 and EP 4 receptors but not EP 1 and EP 3 receptors, are present in prostate cancer cell lines [55, 56]. Thus, the cell lines do not express the same EP receptor subtypes as prostate tumors.…”

“…Thus, the cell lines do not express the same EP receptor subtypes as prostate tumors. The activation of EP 2 , and possibly EP 4 , receptor in PC-3 cells by PGE 2 activates PKA pathway to increase cell growth but are less effective in DU-145 and LNCaP cells [55, 56]. Calcitriol (1,25-dihydroxyvitamin D 3 ) inhibits prostate cancer cell growth and differentiation by down regulating the expression of COX-2 and EP 2 and FP receptors [74–80].…”