Multidrug resistance associated genes MRP1, MRP2 and MRP3 in primary and anthracycline exposed breast cancer

Anticancer Res. 2004 Sep-Oct;24(5A):2931-9.

Abstract

Background: Multidrug resistance associated proteins MRP1, MRP2 and MRP3 confer in vitro multidrug resistance. We investigated their role in breast cancer resistance to anthracycline-based chemotherapy.

Materials and methods: Using real-time reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC), the expression of MRP1 - 3 was quantified in nine breast cancer cell lines and 30 breast carcinoma samples.

Results: MRP1 - 3 mRNA was detectable in all breast cancer cell lines and tumor samples. No increase of expression was detected between untreated carcinoma and post-neoadjuvant anthracycline treatment tumor samples. IHC failed to detect the proteins. MRP1 - 3 expression was not associated with tumor response to treatment or with outcome.

Conclusion: MRP1 - 3 are expressed in breast cancer cells, but are not detected with IHC. We have found no evidence linking these proteins to clinical drug resistance in a small but well-documented series of breast cancer samples.

MeSH terms

  • Anthracyclines / administration & dosage
  • Anthracyclines / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / surgery
  • Cell Line, Tumor
  • Clinical Trials, Phase II as Topic
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Epirubicin / administration & dosage
  • Fluorouracil / administration & dosage
  • Gene Expression / drug effects
  • Genes, MDR / drug effects*
  • Humans
  • Immunohistochemistry
  • Membrane Transport Proteins / biosynthesis
  • Membrane Transport Proteins / genetics
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins / biosynthesis*
  • Multidrug Resistance-Associated Proteins / genetics*
  • Multidrug Resistance-Associated Proteins / metabolism
  • Neoadjuvant Therapy
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics

Substances

  • ABCC2 protein, human
  • Anthracyclines
  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins
  • RNA, Messenger
  • multidrug resistance-associated protein 3
  • Epirubicin
  • Cyclophosphamide
  • Fluorouracil
  • multidrug resistance-associated protein 1

Supplementary concepts

  • FEC protocol