OXYTOCIN INHIBITS THE PROLIFERATION OF MDA-MB231 HUMAN BREAST-CANCER CELLS VIA CYCLIC ADENOSINE-MONOPHOSPHATE AND PROTEIN-KINASE-A

Oxytocin (OT) inhibits the proliferation of breast-cancer cells in vit ro via a specific G-coupled receptor, To elucidate the intracellular m echanism involved in this biological effect, different G-coupled recep tor mediators have been investigated in untreated and OT-treated MDA-M B231 breast-carcinoma cells, In these cells, after OT treatment, a sig nificant cAMP increase was observed using a radioimmunoassay procedure , whereas the Ca2+ (determined with the fluorescent probe fura-2) and the inositol phosphate (determined after cell labeling with myo(2-H-3) -inositol) concentrations were not modified, contrary to what has been observed in myometrial and myo-epithelial cells, The PKA inhibitor PK I (6-22) amide reverted the effect of OT, indicating that the anti-pro liferative effect of the peptide is strictly related to the cAMP-PKA p athway, OT treatment did not modify tyrosine phosphorylation either. O ur results indicate that in breast epithelial cells devoid of contract ile activity, cAMP is the intracellular mediator of OT action, whereas the Ca2+-phosphoinositide system is not involved. Int. I, Cancer 72:3 40344, 1997. (C) 1997 Wiley-Liss, Inc.