title: Divergent Roles of PAX2 in the Etiology and Progression of Ovarian Cancer.
abstract: PAX2 is an essential transcription factor for development. Aberrant PAX2 expression in adult tissues is associated with carcinogenesis and experimental evidence shows that PAX2 generally exhibits oncogenic properties. Although PAX2 is not expressed in normal ovaries, it is highly expressed in low malignant potential and low-grade epithelial ovarian tumors, suggesting that PAX2 induction in ovarian surface epithelium (OSE) may contribute to transformation. Herein, we provide evidence that expression of PAX2 in normal murine OSE cells (mOSE) enhances their proliferation and survival and, with loss of p53, induces tumorigenicity. PAX2 expression in murine ovarian cancer cells enhanced or inhibited tumorigenicity, depending on the model system. In RM cells (mOSE transformed by K-RAS and c-MYC), PAX2 expression inhibited p53 and induced pERK1/2 and COX2, resulting in enhanced angiogenesis and decreased apoptosis of tumors arising from these cells. However, in a murine model of high-grade serous ovarian cancer (STOSE), PAX2 expression improved animal survival by reducing proliferation and metastasis, which correlated with increased Htra1 and decreased COX2. Thus, PAX2 may not be a classical oncogene or tumor suppressor but instead can act in either role by differential regulation of COX2 and/or HTRA1.
authors.affiliation: Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Canada. Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada. King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
authors.forename: Ensaf M
authors.initials: EM
authors.lastname: Al-Hujaily
authors.affiliation: Department of Urology, Affiliated Cancer Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Gynecologic Oncology, Affiliated Cancer Hospital of Guangxi Medical University, Nanning, China.
authors.forename: De-Sheng
authors.initials: DS
authors.lastname: Yao
authors.affiliation: Centre de recherche du Centre hospitalier de l'Université de Montréal, Institut du cancer de Montréal, Montréal, Québec, Canada.
authors.forename: Euridice
authors.initials: E
authors.lastname: Carmona
authors.affiliation: Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Canada.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Garson
authors.affiliation: Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Canada. Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada. bvanderhyden@ohri.ca.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Vanderhyden
mesh_terms: D000818:Animals; D015153:Blotting, Western; D000077216:Carcinoma, Ovarian Epithelial; D049109:Cell Proliferation / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D051762:PAX2 Transcription Factor / Q000378:metabolism*; D034741:RNA, Small Interfering; D059467:Transcriptome; D014162:Transfection
chemical_list: D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; D034741:RNA, Small Interfering