Induction of multidrug resistance (MDR) by transfection of MCF-10A cell line with c-Ha-ras and c-erbB-2 oncogenes

Int J Cancer. 1994 Oct 15;59(2):208-11. doi: 10.1002/ijc.2910590212.

Abstract

To investigate the relationship between oncogene activation and appearance of multidrug resistance (MDR) we transfected the human breast epithelial cell line MCF-10A, negative for the expression of the P-glycoprotein, with c-Ha-ras and/or c-erbB-2 oncogenes. The appearance of the MDR phenotype was then studied by evaluating mdr-1 mRNA expression, the presence of P-glycoprotein on the cell membrane and the onset of doxorubicin resistance, together with the effect of the reversing agent verapamil. We found that only MCF-10A transfected with both c-Ha-ras and c-erbB-2 oncogenes acquired the MDR phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / analysis
  • Base Sequence
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Doxorubicin / pharmacology
  • Drug Resistance, Multiple / genetics*
  • Drug Screening Assays, Antitumor
  • Gene Expression
  • Genes, erbB-2*
  • Genes, ras*
  • Humans
  • Immunohistochemistry
  • Molecular Sequence Data
  • Phenotype
  • Transfection*
  • Tumor Cells, Cultured
  • Verapamil / pharmacology

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Doxorubicin
  • Verapamil