Suppression of the c-erbB-2 gene product decreases transformation abilities but not the proliferation and secretion of proteases of SK-OV-3 ovarian cancer cells.
The overexpression of the c-erbB-2 oncogene product has been reported in approximately 20-30% of human ovarian cancers and has been correlated with a poor prognosis in ovarian cancer patients. To investigate the function of p185(c-erbB-2) in human ovarian cancer cells, a c-erbB-2-specific single-chain antibody (scFv-5R) was expressed in the c-erbB-2-overexpressing SK-OV-3 cell line using a retroviral expression vector. Eight individual clones expressing the single-chain antibody were isolated. These clones have a prominent retention of the cell surface p185(c-erbB-2). In this study we compared the proliferation rate, the anchorage-independent growth, the secretion of matrix metalloproteases and of the urokinase-type plasminogen activator. The clones expressing the c-erbB-2 single-chain antibody, the control cells harbouring the empty vector and the parental SK-OV-3 cells they all had similar proliferation rates in the presence of 10% serum and secreted similar amounts of matrix metalloproteases and of the urokinase-type plasminogen activator. However, the expression of the c-erbB-2 oncogene product offers a strong growth advantage under serum-reduced conditions with 1% serum. In contrast to the parental SK-OV-3 and empty vector control cells, the scFv-5R-expressing clones were not able to grow anchorage-independently. These findings suggest that c-erbB-2 enhances transformation abilities of SK-OV-3 ovarian cancer cells without affecting the secretion of proteases and the proliferation of SK-OV-3 ovarian cancer cells in the presence of high concentrations of serum.
Wiechen
K
K
Institute of Pathology, Universitätsklinikum Charité, Medizinische Fakultät der Humboldt-Universität Berlin, Germany.
Karaaslan
S
S
Turzynski
A
A
Dietel
M
M
D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors*; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007424:Intracellular Fluid / Q000201:enzymology / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D014568:Urokinase-Type Plasminogen Activator