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