Expression and biological role of the prostaglandin D synthase/SOX9 pathway in human ovarian cancer cells

Safia Malki; Frédéric Bibeau; Cécile Notarnicola; Sylvie Roques; Philippe Berta; Francis Poulat; Brigitte Boizet-Bonhoure

doi:10.1016/j.canlet.2007.04.007

Expression and biological role of the prostaglandin D synthase/SOX9 pathway in human ovarian cancer cells

Cancer Lett. 2007 Oct 8;255(2):182-93. doi: 10.1016/j.canlet.2007.04.007. Epub 2007 May 29.

Authors

Safia Malki¹, Frédéric Bibeau, Cécile Notarnicola, Sylvie Roques, Philippe Berta, Francis Poulat, Brigitte Boizet-Bonhoure

Affiliation

¹ Department of Development and Differentiation, Institut de Génétique Humaine IGH CNRS UPR1142, 141, rue de la Cardonille, 34396 Montpellier, Cedex 5, France.

PMID: 17532558
DOI: 10.1016/j.canlet.2007.04.007

Abstract

New therapeutic strategies for ovarian cancer include the identification of involved signaling pathways that could potentially serve as a source of biomarkers for early stages of the disease. In this study, we show that the embryonic male prostaglandin D synthase (Pgds)/SOX9 pathway is expressed at both the RNA and protein levels in different types of human ovarian tumors, pointing to Pgds and SOX9 as possible diagnostic markers for ovarian carcinomas. Using ovarian cancer cell lines, we found, first, that components of the Pgds/SOX9 pathway are expressed in these cells, and second, that treatment of these cells with prostaglandin D2 (PGD2) can inhibit their growth via its DP1 receptor and induce apoptosis. Finally, using siRNA and overexpression strategies, we demonstrate that SOX9 expression is induced by PDG2 and is responsible for PDG2-mediated growth inhibition. Accordingly, as stimulating the PGD2/DP1 signal transduction pathway upregulates SOX9 expression, either activators of this pathway or DP1 agonists may be useful as new therapeutic agents.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis
Biomarkers, Tumor / analysis
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism*
Carcinoma / metabolism*
Carcinoma / pathology
Cell Line, Tumor
Cell Proliferation / drug effects
Female
High Mobility Group Proteins / analysis
High Mobility Group Proteins / genetics
High Mobility Group Proteins / metabolism*
Humans
Intramolecular Oxidoreductases / genetics
Intramolecular Oxidoreductases / metabolism*
Intramolecular Oxidoreductases / pharmacology
Lipocalins
Male
Ovarian Neoplasms / metabolism*
Ovarian Neoplasms / pathology
RNA, Small Interfering / pharmacology
Receptors, Prostaglandin / agonists
SOX9 Transcription Factor
Signal Transduction
Transcription Factors / analysis
Transcription Factors / genetics
Transcription Factors / metabolism*
Up-Regulation

Substances

Biomarkers, Tumor
High Mobility Group Proteins
Lipocalins
RNA, Small Interfering
Receptors, Prostaglandin
SOX9 Transcription Factor
SOX9 protein, human
Transcription Factors
prostanoid D receptor 1, human
Intramolecular Oxidoreductases
prostaglandin R2 D-isomerase