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Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
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Effect of the breast-cancer resistance protein on atypical multidrug resistance

H Lage1, M Dietel

  • 1Institute of Pathology, University Hospital Charité, Humboldt-University Berlin, Germany. hermann.lage@charite.de

The Lancet. Oncology
|March 22, 2002
PubMed

Insights

A novel transporter, breast-cancer resistance protein (BCRP), contributes to atypical multidrug resistance in cancer cells. This finding may impact future chemotherapy strategies by identifying new targets for overcoming drug resistance.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Multidrug resistance (MDR) is a major cause of chemotherapy failure in cancer treatment.
  • Classic MDR is often mediated by P-glycoprotein, an ATP-binding cassette (ABC) transporter.
  • Atypical MDR involves different mechanisms, including novel ABC transporters.

Purpose of the Study:

  • To investigate the role of a novel ABC transporter, breast-cancer resistance protein (BCRP), in atypical multidrug resistance.
  • To characterize the BCRP transporter and its contribution to drug resistance in cancer cell lines.

Main Methods:

  • Analysis of human cancer cell lines with atypical multidrug resistance.
  • Identification and characterization of the novel ABC transporter BCRP.
  • Transfection experiments using BCRP cDNA to transfer the MDR phenotype.

Main Results:

  • Pronounced overexpression of BCRP was observed in cancer cell lines exhibiting atypical multidrug resistance.
  • BCRP is a 655-aminoacid protein that functions as a dimerized ABC half-transporter.
  • Transfection of BCRP cDNA conferred an atypical multidrug-resistant phenotype to drug-sensitive cells.

Conclusions:

  • BCRP is a key mediator of atypical multidrug resistance in cancer.
  • While its clinical role is under investigation, preliminary data suggest BCRP is involved in clinical multidrug resistance.
  • Understanding BCRP's function may lead to novel therapeutic strategies against drug-resistant cancers.

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