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Atypical multidrug resistance: breast cancer resistance protein messenger RNA expression in mitoxantrone-selected

D D Ross1, W Yang, L V Abruzzo

  • 1University of Maryland Greenebaum Cancer Center, Department of Medicine, University of Maryland School of Medicine, and Baltimore Veterans Medical Center, 21201, USA. DROSS@umcc01.umcc.ab.umd.edu

Journal of the National Cancer Institute
|March 10, 1999
PubMed
Abstract

Insights

Drug-resistant cancer cells frequently overexpress Breast Cancer Resistance Protein (BCRP) when exposed to mitoxantrone. This suggests BCRP is a key cellular defense mechanism against this chemotherapy drug.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Pharmacology

Background:

  • Human cancer cell lines develop resistance to mitoxantrone, characterized by reduced drug accumulation.
  • This resistance occurs without increased expression of known drug resistance transporters like P-glycoprotein.
  • Breast Cancer Resistance Protein (BCRP) is a recently identified transporter linked to mitoxantrone and anthracycline resistance.

Purpose of the Study:

  • To investigate the prevalence of BCRP overexpression in cancer cell lines selected for mitoxantrone resistance.

Main Methods:

  • RNA and DNA were isolated from parental and drug-selected cell lines.
  • Northern blot hybridization analyzed BCRP messenger RNA (mRNA) expression.
  • Southern blot hybridization assessed BCRP gene amplification.

Main Results:

  • Mitoxantrone-selected drug-resistant human cancer cell lines (including breast, colon, gastric, fibrosarcoma, and myeloma) showed marked overexpression of BCRP mRNA.
  • Analysis of MCF-7/MX cells revealed amplification of the BCRP gene in BCRP-overexpressing cells.

Conclusions:

  • Frequent overexpression of BCRP mRNA in mitoxantrone-selected multidrug-resistant cell lines indicates BCRP is a significant cellular defense mechanism.
  • BCRP is likely the "mitoxantrone transporter" hypothesized in these resistant cell lines.

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