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Expression of ABC-transport proteins in canine mammary cancer: consequences for chemotherapy

K U Honscha1, A Schirmer, A Reischauer

  • 1Institute of Veterinary Physiology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany. K.honscha@vetmed.uni-leipzig.de

Reproduction in Domestic Animals = Zuchthygiene
|September 17, 2009
PubMed

Insights

Drug resistance in canine mammary tumors is often due to ATP-binding cassette (ABC) transporters. These transporters, including multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP), limit chemotherapy effectiveness.

Area of Science:

  • Veterinary Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Drug resistance is a significant challenge in cancer chemotherapy.
  • ATP-binding cassette (ABC) transporters in tumor cells can prevent the accumulation of chemotherapeutic agents.
  • Understanding ABC transporter expression in canine mammary tumors is crucial for effective treatment.

Purpose of the Study:

  • To investigate the mRNA expression of seven ABC-transporters in canine mammary tumors.
  • To functionally analyze the canine breast cancer resistance protein (cBCRP) and its role in drug resistance.
  • To determine the impact of ABC transporter expression on chemotherapy efficacy in canine mammary cancer.

Main Methods:

  • RT-PCR was used to analyze the mRNA expression of seven ABC-transporters in 103 canine mammary tumor samples.
  • Stable transfection of Madin-Darby canine kidney-II cells with cBCRP was performed.
  • MTT viability assays were conducted to assess drug resistance in transfected cells.

Main Results:

  • All tumor samples expressed multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP).
  • High expression rates were observed for MRP7 (97.1%), MRP3 (96.1%), Pgp (92.2%), MRP5 (85.4%), and MRP6 (64.1%).
  • cBCRP-transfected cells exhibited a 5.4-fold resistance to doxorubicin, while methotrexate sensitivity remained unaffected.

Conclusions:

  • The expression of seven different ABC-transporters can contribute to the lack of chemotherapy efficacy in canine mammary cancer.
  • Given its universal expression in canine mammary tumors and induced doxorubicin resistance, cBCRP is a key factor.
  • Doxorubicin may be an inappropriate choice for treating canine mammary cancer due to cBCRP-mediated resistance.

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