Oncotarget

Research Papers:

Role of PAR-4 in ovarian cancer

Sonia Meynier _, Marianne Kramer, Pascale Ribaux, Jean Christophe Tille, Florence Delie, Patrick Petignat and Marie Cohen

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Oncotarget. 2015; 6:22641-22652. https://doi.org/10.18632/oncotarget.4010

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Abstract

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

Correspondence to:

Marie Cohen, e-mail: marie.cohen@hcuge.ch

Keywords: PAR-4, GRP78, ovarian cancer, apoptosis

Received: January 13, 2015     Accepted: May 14, 2015     Published: May 27, 2015

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.


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