Integrin regulation of beta-catenin signaling in ovarian carcinoma [abstract]
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In 2006, there were 20,180 new cases of epithelial ovarian carcinoma and less than 30% of patients survive 5 years after developing distant metastases. Based on these statistics, the need for elucidation of the mechanisms that underlie ovarian tumor cell metastasis is crucial. Ovarian tumor cell adhesion to and invasion through the mesothelial layer and sub-mesothelial matrix of peritoneal organs are dependent on differential regulation of cell-cell and cell-matrix signaling, modulated by E-cadherin and 1 integrins, respectively. Mimicking cell-matrix contact with 1 integrin antibody-coated micro-beads ( 1 beads) has previously demonstrated a 50% decrease in surface E cadherin expression, suggesting that cell-matrix interaction downregulates cell-cell contact. Initial studies show up-regulation of urinary-type plasminogen activator (uPA) and matrix metalloproteinase 9 (MMP-9) following 1bead-induced integrin aggregation. As the promoters for both uPA and MMP-9 contain Tcf/Lef binding elements, current studies will investigate the fate of -catenin following integrin-mediated disruption of adherens junctions, and regulation of - catenin-dependent transcriptional activity. This includes analysis of -catenin nuclear translocation and transcriptional profiling of -catenin target genes by quantitative RT-RTPCR.