title: COX2 and PGE2 mediate EGF-induced E-cadherin-independent human ovarian cancer cell invasion.
abstract: Elevated expression of cyclooxygenase 2 (COX2 (PTGS2)) has been reported to occur in human ovarian cancer and to be associated with poor prognosis. We have previously demonstrated that COX2-derived prostaglandin E2 (PGE2) promotes human ovarian cancer cell invasion. We had also demonstrated that epidermal growth factor (EGF) induces human ovarian cancer cell invasion by downregulating the expression of E-cadherin through various signaling pathways. However, it remains unclear whether COX2 and PGE2 are involved in the EGF-induced downregulation of E-cadherin expression and cell invasion in human ovarian cancer cells. In this study, we showed that EGF treatment induces COX2 expression and PGE2 production in SKOV3 and OVCAR5 human ovarian cancer cell lines. Interestingly, COX2 is not required for the EGF-induced downregulation of E-cadherin expression. In addition, EGF treatment activates the phosphatidylinositol-3-kinase (PI3K)/Akt and cAMP response element-binding protein (CREB) signaling pathways, while only the PI3K/Akt pathway is involved in EGF-induced COX2 expression. Moreover, we also showed that EGF-induced cell invasion is attenuated by treatment with a selective COX2 inhibitor, NS-398, as well as PGE2 siRNA. This study demonstrates an important role for COX2 and its derivative, PGE2, in the mediation of the effects of EGF on human ovarian cancer cell invasion.
authors: Department of Obstetrics and GynaecologyChild and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4.
authors: Xin
authors: X
authors: Qiu
authors: Department of Obstetrics and GynaecologyChild and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4.
authors: Jung-Chien
authors: JC
authors: Cheng
authors: Department of Obstetrics and GynaecologyChild and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4.
authors: Hsun-Ming
authors: HM
authors: Chang
authors: Department of Obstetrics and GynaecologyChild and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4 peter.leung@ubc.ca.
authors: Peter C K
authors: PC
authors: Leung
mesh_terms: D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D006801:Humans; D009361:Neoplasm Invasiveness; D009578:Nitrobenzenes / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D015820:Cadherins; D052246:Cyclooxygenase 2 Inhibitors; D009578:Nitrobenzenes; D034741:RNA, Small Interfering; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D004815:Epidermal Growth Factor; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone
keywords: COX2; EGF; PGE2; ovarian cancer