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

Br J Cancer. 1999 Nov;81(5):790-5. doi: 10.1038/sj.bjc.6690765.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / antagonists & inhibitors*
  • Cell Division / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology*
  • Female
  • Humans
  • Intracellular Fluid / enzymology
  • Intracellular Fluid / metabolism
  • Matrix Metalloproteinase Inhibitors
  • Matrix Metalloproteinases / metabolism*
  • Ovarian Neoplasms / enzymology*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / biosynthesis*
  • Receptor, ErbB-2 / genetics
  • Tumor Cells, Cultured
  • Urokinase-Type Plasminogen Activator / antagonists & inhibitors
  • Urokinase-Type Plasminogen Activator / metabolism*

Substances

  • Antineoplastic Agents
  • Matrix Metalloproteinase Inhibitors
  • Receptor, ErbB-2
  • Urokinase-Type Plasminogen Activator
  • Matrix Metalloproteinases