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 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.
Wiechen
K
K
Institute of Pathology, Universitätsklinikum Charité, Medizinische Fakultät der Humboldt-Universität, Berlin, Germany. kai.wiechen@charite.de
Karaaslan
S
S
Dietel
M
M
D002465:Cell Movement / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D010051:Ovarian Neoplasms / Q000473:pathology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D017228:Hepatocyte Growth Factor; D018719:Erb-b2 Receptor Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate