Isolation and characterization of an adriamycin-resistant breast tumor cell line

In Vitro Cell Dev Biol. 1990 Jun;26(6):621-8. doi: 10.1007/BF02624212.

Abstract

An adriamycin-resistant human breast tumor cell line MDA-A1R was generated by step-wise selection in increasing concentrations of drug from the parent cell line MDA-MB-231. MDA-A1R cells grow as loosely attached cell aggregates with a doubling time of 28-32 h; the MDA-MB-231 parent cell line grows as a standard monolayer culture with a 20-h doubling time. The MDA-A1R cell line is highly resistant to adriamycin compared to the parent cell line, and is cross-resistant to velban and colchicine suggestive of a multidrug resistance (MDR) phenotype. MDA-A1R cells exhibit reduced net adriamycin content as compared to the parent cell line. The MDR-associated P-glycoprotein gene is amplified approximately 10- to 30-fold in MDA-A1R cells. P-glycoprotein sequences are overexpressed in the resistant cells and are stable for up to 13 wk after drug removal. Moreover, MDA-A1R cells show the presence of very high levels of P-glycoprotein. MDA-A1R is thus an in vitro model system to study the mechanism of MDR in human breast cancer.

Publication types

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

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Adenocarcinoma
  • Blotting, Southern
  • Breast Neoplasms
  • Cell Aggregation
  • Cell Division / drug effects
  • Cell Line
  • Colchicine / pharmacology
  • Culture Techniques / methods
  • Doxorubicin / metabolism
  • Doxorubicin / pharmacology*
  • Drug Resistance* / genetics
  • Female
  • Gene Amplification
  • Humans
  • Kinetics
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / isolation & purification
  • Tumor Cells, Cultured / cytology*
  • Tumor Cells, Cultured / drug effects
  • Vinblastine / pharmacology

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Membrane Glycoproteins
  • Vinblastine
  • Doxorubicin
  • Colchicine