Abstract
Abstract SOX2 encodes a member of the SRY-related HMG-box (SOX) family of transcription factors involved in the regulation of embryonic development and in the determination of cell fate. SOX2 maps to 3q26.33, a region frequently amplified in HGSOvCa as reported in the TCGA and other large array-based CGH studies. However, the role of SOX2 in HGSOvCa oncogenesis and progression has not been studied yet. Given the importance of SOX2 in maintenance of stem cell phenotype and its overexpression in solid tumors, we sought to define the role of SOX2 in HGSOvCa. In order to establish a direct role for SOX2 in vivo, we conducted DNA copy number analysis and qRT-PCR analysis in two independent panels of primary HGSOvCa and 25 serous OVCA lines. We overexpressed SOX2 in T29, OVCA433, A2780, SKOV3 and OVCAR5 cells and/or knockdown SOX2 in UCI101 and OV90 cells. Ectopic expression of SOX2 resulted in decreased cell proliferation, soft agar colony formation, in vivo tumorigenicity but higher degree of invasion relative to cells with empty vectors. SOX2 overexpression increased MMP2 activity as determined by gelatin zymography. We also performed mRNA profiling to identify SOX2 target genes. SOX2 knockdown cells decreased migration,andinvasion but increased tumorigenicity. Differentially expressed genes in cells overexpressing SOX2 will be presented. Increased SOX2 expression in HGSOvCa appears to produce a more invasive yet quiestant cell. Overexpression of SOX2 may induce a stem-like transcriptional program in HGSOvCa. Thus, identifying SOX2 target genes may offer new insight into the understanding of ovarian cancer biology. Citation Format: Gayatry Mohapatra, Junko Kikuchi, Michael J. Birrer. SOX2 contributes towards invasive phenotype of serous ovarian cancer by up-regulating MMP2. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2997. doi:10.1158/1538-7445.AM2013-2997
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