Divergent Roles of PAX2 in the Etiology and Progression of Ovarian Cancer

作者：Al-Hujaily, Ensaf M.; Tang, Yong; Yao, De-Sheng; Carmona, Euridice; Garson, Kenneth; Vanderhyden, Barbara C.^*

来源：Cancer Prevention Research, 2015, 8(12): 1163-1173.

DOI：10.1158/1940-6207.CAPR-15-0121-T

• SURFACE EPITHELIUM
• COLON-CANCER
• CYCLIN D1
• EXPRESSION
• GENES
• P53
• CELLS
• PROLIFERATION
• RESISTANCE
• PTEN

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 OSEcells (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.

• 出版日期2015-12
• 单位广西医科大学