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- W1499174450 abstract "EpCAM is a cell-surface glycoprotein that is overexpressed in the majority of epithelial cancers. However, the functional role of EpCAM in the process of neoplastic transformation remains unclear. The literature is inconsistent, with in vitro studies demonstrating that EpCAM expression is associated with either increased or decreased invasion depending on the cancer type. Further, EpCAM expression in primary tumor specimens as measured by immunohistochemistry is associated with either favorable or unfavorable prognosis depending on the cancer type. To study the role of EpCAM in cancer invasion in more detail, we manipulated EpCAM expression in loss-of-function and gain-of-function studies and demonstrate that EpCAM expression is directly correlated with invasion in breast cancer cells, and inversely correlated with invasion in gastrointestinal cancer cells. In parallel studies using luciferase-based pathway reporter constructs, we demonstrate that EpCAM expression is differentially associated with AP-1, Myc, and NF-KB transcriptional activity (increased in breast cancer cells, and decreased in gastrointestinal cancer cells). Finally, gene expression profiling and confirmatory real-time RT-PCR analyses demonstrate concomitant and differential alterations in the transcriptional activity of a number of several known AP-1 and Myc target genes involved in cancer invasion including EGFR, ARPC1B, DNMT1 and MMP1. Taken together, these data are the first demonstration that EpCAM expression can influence AP-1 and NF-KB transcriptional activity, and strongly suggest that the differential impact of EpCAM on cancer invasion is mediated through these transcriptional factors. These data also have important implications for the application of molecular therapies that are currently under development targeting EpCAM in epithelial carcinomas. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-279." @default.
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- W1499174450 date "2009-05-01" @default.
- W1499174450 modified "2023-09-23" @default.
- W1499174450 title "Abstract #LB-279: Differential impact of EpCAM on cancer invasion in barest and gastrointestinal cancers in association with altered AP-1 and C-myc transcriptional activity" @default.
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