lvement of the Gi-Coupled Signaling Pathway

Downlo ression of genes that encode oxytocin (OXT) and vasopressin (AVP) and their cognate receptors in normal seased prostates are only partially characterized. Reverse transcription and PCR were used to examine the sion of these genes in normal prostate epithelial and stromal cell lines, k-ras–transformed prostate epithel lines, and in four prostate cancer cell lines. Secreted and cell-associated OXT peptide was measured by yme immunoassay. OXT and its receptor (OXTR) were expressed in all eight prostate cell lines. Cellted OXT peptide was also found in all prostate epithelial cell lines except in DU145 cells. Neither AVP cognate receptors (V1a receptor and V2 receptor) were expressed in any prostate cell line examined. data point to the OXTR as the primary target of OXT and AVP, and suggest that OXT might be an ine/paracrine regulator in human prostate. We found that OXT induces the migration of PC3 and , but not DU145 prostate cancer cells. The effect of OXT is distinct from the epidermal growth factor –induced migration of prostate cancer cells, in which ERK1/2 and EGF receptor kinase activities were ed. When cells were pretreated with pertussis toxin, the effect of OXT, but not EGF, on cell migration was ed. Pretreatment with the cyclic AMP analogue, 8-Br-cAMP, did not affect OXT-induced cell migration, eliminated the nonspecific effect of pertussis toxin. We conclude that a Gi-dependent mechanism is inwhich volved in OXTR-mediated migration of prostate cancer cells, and indicates a role for OXTR in prostate cancer metastasis. Mol Cancer Res; 8(8); 1164–72. ©2010 AACR.