Involvement of the c-erbB-2 oncogene product in the EGF-induced cell motility of SK-OV-3 ovarian cancer cells

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 pro duct (p185(c-erbB-2)). To investigate the role of p185(c-erbB-2) in cell mo tility, a c-erbB-2-specific single-chain antibody was expressed in SK-OV-3 cells using a retroviral expression vector. Eight individual clones express ing the single chain antibody were isolated. These clones have prominent re tention of the cell-surface p185(c-erbB-2). The EGF-induced morphologic cha nges and cell motility of the single-chain-anti body-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 t he motility signal elicited by 12-O-tetradecanoyl-phorbol-13-acetate. These data indicate that the c-erbB-2 oncogene product is essential to mediate t he motility signal of EGF to SK-OV-3 ovarian cancer cells. The enhancement of tumor-cell motility may be partially responsible for the unfavorable pro gnosis of ovarian cancer with over-expression of c-erbB-2. (C) 1999 Wiley-L iss, Inc.