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 ap proximately 20-30% of human ovarian cancers and has been correlated with a poor prognosis in ovarian cancer patients. To investigate the function of p 185(c-erbB-2) in human ovarian cancer cells, a c-erbB-2-specific single-cha in antibody (scFv-5R) was expressed in the c-erbB-2-overexpressing SK-OV-3 cell line using a retroviral expression vector. Eight individual clones exp ressing the single-chain antibody were isolated. These clones have a promin ent retention of the cell surface p185(c-erbB-2). I, this study we compared the proliferation rate, the anchorage-independent growth, the secretion of matrix metalloproteases and of the urokinase-type plasminogen activator. T he 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 sim ilar proliferation rates in the presence of 10% serum and secreted similar amounts of matrix metalloproteases and of the urokinase-type plasminogen ac tivator. However, the expression of the c-erbB-2 oncogene product offers a strong growth advantage under serum-reduced conditions with 1% serum. In co ntrast to the parental SK-OV-3 and empty vector control cells, the scFv-5R- expressing clones were not able to grow anchorage-independently. These find ings suggest that c-erbB-2 enhances transformation abilities of SK-OV-3 ova rian cancer cells without affecting the secretion of proteases and the prol iferation of SK-OV-3 ovarian cancer cells in the presence of high concentra tions of serum. (C) 1999 Cancer Research Campaign.