The Carcinoma-associated Antigen EpCAM Induces Glyoxalase 1 Resulting in Enhanced Methylglyoxal Turnover

摘要

Background: The epithelial cell adhesion molecule (EpCAM) is a homophilic adhesion molecule expressed de novo on a variety of epithelial tumors. Overexpression of EpCAM results in enhanced proliferation and rapid induction of the proto-oncogene c-myc. Materials and Methods: The novel proteomics-based fluorescence difference gel electrophoresis (DIGE technology) was used to study EpCAM effects on the proteome of human epithelial cells. Results: DIGE analysis resulted in the identification of five proteins with a significantly changed regulation ranging from -1.3 to +5.8-fold. One of the identified proteins, namely glyoxalase 1, experienced a shift in the isoelectric point from pH 5.2 to 5.0 upon EpCAM expression. This shift correlated with a gain of enzymatic activity of glyoxalase 1 resulting in an enhanced methylglyoxal turnover. Conclusion: We show the potential of the DIGE technology to rapidly and quantitatively analyze proteomes for changed expression levels and, importantly, posttranslational modifications. Furthermore, we describe new targets of the carcinoma antigen EpCAM including glyoxalase1.