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Expression profiling of ABC transporters in a drug-resistant breast cancer cell line using AmpArray

Yang Liu1, Hui Peng, Jian-Ting Zhang

  • 1IU Cancer Center, Indiana University School of Medicine, 1044 W. Walnut Street, R4-166, Indianapolis, IN 46202, USA.

Molecular Pharmacology
|May 20, 2005
PubMed

Insights

Multidrug resistance (MDR) in cancer involves more than just ABCG2. This study found other ATP-binding cassette (ABC) transporters, like ABCA4 and ABCC3, also contribute to MDR in MCF7/AdVp3000 cells, suggesting new therapeutic targets.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • ATP-binding cassette (ABC) transporters are a superfamily of membrane proteins involved in transporting various substrates.
  • Overexpression of certain human ABC transporters, such as ABCB1 and ABCC1, is linked to multidrug resistance (MDR) in cancer chemotherapy.
  • Previous research suggested ABCG2 overexpression caused MDR in the MCF7/AdVp3000 cell line, but this alone did not fully explain the observed resistance levels.

Purpose of the Study:

  • To investigate the comprehensive expression profile of ABC transporters in the multidrug-resistant MCF7/AdVp3000 cell line.
  • To identify other ABC transporters, beyond ABCG2, that may contribute to the MDR phenotype in this cell line.
  • To evaluate the utility of AmpArray analysis for profiling ABC transporter expression in resistant cell lines and tumors.

Main Methods:

  • Utilized AmpArray analysis to profile the expression of ABC transporters in MCF7/AdVp3000 cells compared to parental MCF7 cells.
  • Quantified fold-changes in expression for individual ABC transporters.
  • Performed gene silencing of ABCC3 in MCF7/AdVp3000 cells to assess its impact on doxorubicin resistance.

Main Results:

  • AmpArray analysis revealed altered expression in 16 ABC transporters in MCF7/AdVp3000 cells compared to MCF7 cells (fold-change ≥ 1.5).
  • Significant increases in expression were observed for ABCA4 (132-fold), ABCC3 (459-fold), and ABCG2 (~3000-fold).
  • Silencing ABCC3 expression in MCF7/AdVp3000 cells led to a significant reduction in doxorubicin resistance, and elevated expression of these transporters reversed with the drug resistance phenotype.

Conclusions:

  • Multidrug resistance in MCF7/AdVp3000 cells is likely mediated by the concerted action of multiple ABC transporters, including ABCA4 and ABCC3, in addition to ABCG2.
  • The findings suggest that targeting multiple ABC transporters may be a viable strategy for overcoming MDR in cancer.
  • AmpArray analysis is presented as an efficient tool for profiling ABC transporter expression, aiding in the potential for individualized cancer therapy design.

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