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

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.
Authors	Safia Malki, Frédéric Bibeau, Cécile Notarnicola, Sylvie Roques, Philippe Berta, Francis Poulat, Brigitte Boizet-Bonhoure
Journal	Cancer letters (Cancer Lett) Vol. 255 Issue 2 Pg. 182-93 (Oct 08 2007) ISSN: 0304-3835 [Print] Ireland
PMID	17532558 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	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
Topics	Apoptosis Biomarkers, Tumor (analysis, genetics, metabolism) Carcinoma (metabolism, pathology) Cell Line, Tumor Cell Proliferation (drug effects) Female High Mobility Group Proteins (analysis, genetics, metabolism) Humans Intramolecular Oxidoreductases (genetics, metabolism, pharmacology) Lipocalins Male Ovarian Neoplasms (metabolism, pathology) RNA, Small Interfering (pharmacology) Receptors, Prostaglandin (agonists) SOX9 Transcription Factor Signal Transduction Transcription Factors (analysis, genetics, metabolism) Up-Regulation

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