title: Role of PAR-4 in ovarian cancer.
abstract: Prostate apoptosis response-4 (PAR-4) is considered as a tumour suppressor due to its ability to selectively induce cell apoptosis in most cancer cells. However little is known about the role of PAR-4 in ovarian cancer. In this study, we investigated for the first time the role of PAR-4 in ovarian carcinogenesis. We showed that PAR-4 mRNA level is not significantly different between healthy and cancer ovarian cells. Immunohistochemistry on ovarian tissue showed that ovarian cancer cells are positive for PAR-4 nuclear and cytoplasmic staining whereas ovarian healthy cells are negative for PAR-4 nuclear staining. We then studied the role of PAR-4 in cell apoptosis. We determined that PAR-4 induces cell apoptosis in response to stimuli, in vitro, but is also involved in the relocation of GRP78 from endoplasmic reticulum to the cell surface of ovarian cancer cell line (SKOV-3 cells). In ovo, PAR-4 decreases ovarian tumour development and increases the response to taxol treatment. These observations suggest that PAR-4 is a very interesting therapeutic target against ovarian carcinogenesis.
authors.affiliation: Department of Gynecology Obstetrics, Faculty of Medicine, University of Geneva, Switzerland.
authors.forename: Sonia
authors.initials: S
authors.lastname: Meynier
authors.affiliation: Department of Gynecology Obstetrics, Faculty of Medicine, University of Geneva, Switzerland.
authors.forename: Marianne
authors.initials: M
authors.lastname: Kramer
authors.affiliation: Department of Gynecology Obstetrics, Faculty of Medicine, University of Geneva, Switzerland.
authors.forename: Pascale
authors.initials: P
authors.lastname: Ribaux
authors.affiliation: Division of Clinical Pathology, Geneva University Hospital, University of Geneva, Switzerland.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Tille
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Switzerland.
authors.forename: Florence
authors.initials: F
authors.lastname: Delie
authors.affiliation: Department of Gynecology Obstetrics, Faculty of Medicine, University of Geneva, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Petignat
authors.affiliation: Department of Gynecology Obstetrics, Faculty of Medicine, University of Geneva, Switzerland.
authors.forename: Marie
authors.initials: M
authors.lastname: Cohen
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002642:Chick Embryo; D004721:Endoplasmic Reticulum / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; C101296:prostate apoptosis response-4 protein; D017239:Paclitaxel
keywords: GRP78; PAR-4; apoptosis; ovarian cancer