| Summary: | Cells of the human ovarian surface epithelium (OSE) are plastic and
uncommitted. Specifically, OSE cells do not express E-cadherin and they can shift
between epithelial and stationary or mesenchymal and migratory phenotypes. In contrast,
well differentiated, low grade ovarian carcinomas, which are thought to arise from the
OSE, express E-cadherin and they display a committed epithelial phenotype. E-cadherin
expression and stationary epithelial commitment are first observed in OSE-derived
inclusion cysts and clefts which are thought to be weakly pre-neoplastic. Therefore, I
determined if forced E-cadherin expression in OSE cells was capable of inducing this
commitment to a stationary epithelial phenotype that is a hallmark of the earliest stages of
ovarian carcinoma formation.
High levels of forced E-cadherin expression in an immortalized human OSE cell
line achieved by stable transfection induced the localization of E-cadherin, P-catenin, and
f-actin to sites of cell-cell contact. High levels E-cadherin also resulted in an increase in
the amount of P-catenin associated with the cytoskeleton formation and a decrease in
LEF-l/p-catenin signaling. Taken together, these data indicate that high levels of forced
E-cadherin expression induced the formation of functional epithelial junctions in
immortalized OSE cells. In addition, these cells had migratory capabilities in threedimensional
basement membrane gels compared to controls and low E-cadherin
expressors. This strongly suggests that E-cadherin is capable of inducing a stationary
epithelial phenotype in human OSE cells.
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