Cisplatin and phorbol ester independently induce ERCC-1 protein in human ovarian carcinoma cells

Int J Oncol. 1998 Nov;13(5):987-92. doi: 10.3892/ijo.13.5.987.

Abstract

Nucleotide excision repair (NER) is the DNA repair pathway by which cisplatin-induced damage is removed from DNA in human cells. ERCC-1 is one of the essential proteins in NER, and is essential for life. Enhanced ERCC-1 expression has been associated with clinical and cellular resistance to cisplatin. We therefore carried out this study to investigate the effect of cisplatin on ERCC-1 protein expression in A2780/CP70 human ovarian cancer cells. Western blot analysis showed that ERCC-1 protein levels were increased to more than 3 times control after a 1 h cisplatin exposure to A2780/CP70 cells in culture. This increase was time- and concentration-dependent. The effect of cisplatin was maximal at 40 mM and peaked 24-48 h after exposure to the drug. These results extend our previous observations that ERCC-1 mRNA expression is induced by cisplatin in this system. TPA, a known AP-1 activator and tumor-promoting phorbol ester, also induced ERCC-1 protein to the same extent as cisplatin, but did not synergize with cisplatin in this regard. These findings suggest that ERCC-1 gene up-regulation in these cells can result through a DNA damage-response pathway, or through the induction of AP-1 activity, independent of the occurrence of DNA damage.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Blotting, Western
  • Carcinogens / pharmacology
  • Cisplatin / pharmacology*
  • DNA-Binding Proteins*
  • Endonucleases*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Proteins / biosynthesis
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Protein Biosynthesis*
  • Proteins / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Carcinogens
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • Proteins
  • ERCC1 protein, human
  • Endonucleases
  • Tetradecanoylphorbol Acetate
  • Cisplatin