The epidermal growth factor (EGF) induces the rapid formation of dendritic processes and the dissociation of SK-OV-3 ovarian cancer cells. The SK-OV-3 cell line is characterized by over-expression of the c-erbB-2 oncogene product (p185(c-erbB-2)). To investigate the role of p185(c-erbB-2) in cell motility, a c-erbB-2-specific single-chain antibody was expressed in SK-OV-3 cells using a retroviral expression vector. Eight individual clones expressing the single chain antibody were isolated. These clones have prominent retention of the cell-surface p185(c-erbB-2). The EGF-induced morphologic changes and cell motility of the single-chain-antibody-expressing clones were strongly inhibited, as observed in cell dissociation and in transmigration experiments. However, the suppression of p185(c-erbB-2) does not inhibit the motility signal elicited by 12-O-tetradecanoyl-phorbol-13-acetate. These data indicate that the c-erbB-2 oncogene product is essential to mediate the motility signal of EGF to SK-OV-3 ovarian cancer cells. The enhancement of tumor-cell motility may be partially responsible for the unfavorable prognosis of ovarian cancer with over-expression of c-erbB-2.
Copyright 1999 Wiley-Liss, Inc.