Abstract 363A: PAX2 is an oncogene in type I ovarian cancer

Ovarian cancer is the second most common gynecologic malignancy, but the most lethal gynecologic cancer. Ovarian cancer is divided into Type I and Type II subgroups. Type I tumors include low-grade micropapillary serous carcinoma, mucinous, endometrioid, and clear cell carcinomas and are characterized by high frequency of KRAS, BRAF, PTEN, or beta-catenin mutations. Type II tumors include high-grade serous carcinoma, malignant mixed mesodermal tumors (carcinosarcomas) and undifferentiated carcinomas and are characterized by high genetic instability and high frequency of TP53 mutation. Using gene expression profiling, we found that Pax2, a transcription factor of the Pax gene family, is highly expressed in type I ovarian tumors but is less expressed in Type II tumors. Pax2 is one of the nine Pax genes which have a conserved DNA sequence motif called the paired box, a 128 amino acid domain in the amino-terminal portion of the protein. Pax2 regulates tissue development and cellular differentiation in embryos and Pax2 expression is attenuated after development. Unattenuated Pax2 expression has been found in several cancer types, but the function of Pax2 in ovarian cancer is not clearly understood. In this study, we further validated the expression of Pax2 in Type I ovarian cancer by immunohistochemistry, western blot analysis and quantitative real-time PCR. Furthermore, the expression of Pax2 in two Type I ovarian cancer cell lines (RMUGL and TOV21G) was knockdown by Pax2 specific shRNA. By comparing to the control non-target shRNA cancer cell lines and the parental cell lines, Pax2 knockdown cell lines have significant reduction in growth rate as measured by WST cell proliferation assay. From the gene expression profiles of three independent Pax2 knockdown cell lines, we identified 196 genes that were significantly affected by the down-regulation of Pax2. Many of these genes are involved in cell cycle control, cellular growth and proliferation, and the TP53 pathway such as BBC3, CHEK1, GADD45A and GADD45B and JUN genes. This suggests that Pax2 may play an oncogenic role in the pathogenesis of ovarian cancer through a TP53-dependent pathway. Since immunotherapy targeting Pax2 is currently being developed, Pax2 could be a therapeutic target for Type I ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 363A.