Role of PAR-4 in ovarian cancer
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Sonia Meynier1, Marianne Kramer1, Pascale Ribaux1, Jean-Christophe Tille2, Florence Delie3, Patrick Petignat1, Marie Cohen1
1Department of Gynecology Obstetrics, Faculty of Medicine, University of Geneva, Switzerland
2Division of Clinical Pathology, Geneva University Hospital, University of Geneva, Switzerland
3School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Switzerland
Marie Cohen, e-mail: [email protected]
Keywords: PAR-4, GRP78, ovarian cancer, apoptosis
Received: January 13, 2015 Accepted: May 14, 2015 Published: May 27, 2015
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.
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