Roth Writ signaling and prostaglandin E-2 (PGE(2)) play pivotal roles in bone development, remodeling, osteoporosis and prostate cancer (PCa) bone metastases We investigated the effects of PGE(2) on Wnt signaling in osteoblast-lineage cells and Wilt-inhibitor expression in PCa cells We demonstrate that low close PGE(2) (0 1 mu M) promotes Writ signaling while higher doses of PGE(2) (10-10 mu M) inhibit these same parameters in osteoblast-lineage cells. The differential effects of low vs high-dose PGE(2) on pre-osteoblasts may be attributed to dose-dependent modulation of prostaglandin receptor (EP) subtype expression, with lower doses increasing the expression the cAMP-stimulatory EP4 receptor subtype and higher closes increasing the expression of the cAMP-inhibitory EP3 receptor subtype Moreover, we demonstrate that high expression levels of COX-2 and PGE(2) promote the secretion of Wnt inhibitors from prostate cancel cells These data demonstrate that there are dose-dependent effects of PGE(2) on Writ activation in osteoblast-lineage cells and Writ-inhibitor expression in PCa cells which may have clinical implications in the management (C) 2010 Elsevier Inc. All rights reserved