Expression and biological role of the prostaglandin D synthase/SOX9 pathway in human ovarian cancer cells.
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.
Malki
Safia
S
Department of Development and Differentiation, Institut de Génétique Humaine IGH CNRS UPR1142, 141, rue de la Cardonille, 34396 Montpellier, Cedex 5, France.
Bibeau
Frédéric
F
Notarnicola
Cécile
C
Roques
Sylvie
S
Berta
Philippe
P
Poulat
Francis
F
Boizet-Bonhoure
Brigitte
B
D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006609:High Mobility Group Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D054834:Lipocalins; D008297:Male; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000819:agonists; D055758:SOX9 Transcription Factor; D015398:Signal Transduction; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D006609:High Mobility Group Proteins; D054834:Lipocalins; D034741:RNA, Small Interfering; D011982:Receptors, Prostaglandin; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D014157:Transcription Factors; C501562:prostanoid D receptor 1, human; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase