| A mutant constitutively active epidermal growth factor receptor (EGFRvIII) is detected at a high frequency in ovarian cancer (75%). This study investigated the role of EGFRvIII in ovarian cancer cell dissociation. Expression of EGFRvIII in an ovarian cancer cell line resulted in: (1) a dispersed phenotype with decreased cell-cell attachments that was reversible to an epithelial one by selectively inhibiting EGFR activation; (2) decreased in vitro proliferation; (3) a changed profile of extracellular matrix-degrading proteases including metalloproteinase-9 (MMP-9), MMP-2, MMP-7, and urokinase plasminogen activator; (4) loss or reduced levels of the junctional proteins E-cadherin, β-catenin, and plakoglobin; (5) altered levels of several gene transcripts involved in dissociation of cancer cells as detected by oligonucleotide microarrays analysis, including proteases, protease inhibitors, cadherins, integrins and several other adhesion molecules; (6) increased phosphorylation of erbB2. In summary, the expression of EGFRvIII in ovarian carcinoma appears to contribute to a more aggressive ovarian carcinoma. |
