title: Oxytocin increases invasive properties of endometrial cancer cells through phosphatidylinositol 3-kinase/AKT-dependent up-regulation of cyclooxygenase-1, -2, and X-linked inhibitor of apoptosis protein.
abstract: Traditionally, oxytocin (OT) is well known to play a crucial role in the regulation of cyclic changes in the uterus, implantation of the embryo, and parturition. Recently, an additional role for OT has been identified in several types of cancer cells in which OT acts as a growth regulator. In endometrial cancer cells, OT is known to efficiently inhibit cellular proliferation. In the present study, we show that OT increases invasiveness of human endometrial carcinoma (HEC) cells, which are otherwise resistant to the growth-inhibiting effects of OT. Using pharmacological inhibitors, invasion assay, RNA interference, and immunofluorescence, we found that OT enhances the invasive properties of HEC cells through up-regulation of X-linked inhibitor of apoptosis protein (XIAP), matrix-metalloproteinase 2 (MMP2), and matrix-metalloproteinase 14 (MMP14). In addition, we show that OT-mediated invasion is both cyclooxygenase 1 (PTGS1) and cyclooxygenase-2 (PTGS2) dependent via the phosphatidylinositol 3-kinase/AKT (PIK3/AKT) pathway. PTGS2 knockdown by shRNA resulted in XIAP down-regulation. We also show that OT receptor is overexpressed in grade I to III endometrial cancer. Taken together, our results describe for the first time a novel role for OT in endometrial cancer cell invasion.
authors.affiliation: Research Group in Molecular Oncology and Endocrinology, Department of Chemistry and Biology, Université du Québec à Trois-Rivières, Trois-Rivières, Québec, Canada.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Déry
authors.forename: Parvesh
authors.initials: P
authors.lastname: Chaudhry
authors.forename: Valérie
authors.initials: V
authors.lastname: Leblanc
authors.forename: Sophie
authors.initials: S
authors.lastname: Parent
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Fortier
authors.forename: Eric
authors.initials: E
authors.lastname: Asselin
mesh_terms: D002277:Carcinoma / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000473:pathology; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010121:Oxytocin / Q000502:physiology*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018045:Receptors, Oxytocin / Q000378:metabolism; D015854:Up-Regulation; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
chemical_list: D007527:Isoenzymes; C569600:OXTR protein, human; D018045:Receptors, Oxytocin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D010121:Oxytocin; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14; D015232:Dinoprostone