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
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Anthracyclines / administration & dosage
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Anthracyclines / pharmacology*
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism*
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Breast Neoplasms / surgery
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Cell Line, Tumor
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Clinical Trials, Phase II as Topic
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Cyclophosphamide / administration & dosage
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Disease-Free Survival
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Drug Resistance, Neoplasm
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Epirubicin / administration & dosage
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Fluorouracil / administration & dosage
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Gene Expression / drug effects
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Genes, MDR / drug effects*
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Humans
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Immunohistochemistry
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Membrane Transport Proteins / biosynthesis
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Membrane Transport Proteins / genetics
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Multidrug Resistance-Associated Protein 2
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Multidrug Resistance-Associated Proteins / biosynthesis*
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Multidrug Resistance-Associated Proteins / genetics*
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Multidrug Resistance-Associated Proteins / metabolism
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Neoadjuvant Therapy
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
Substances
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ABCC2 protein, human
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Anthracyclines
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Membrane Transport Proteins
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Multidrug Resistance-Associated Protein 2
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Multidrug Resistance-Associated Proteins
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RNA, Messenger
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multidrug resistance-associated protein 3
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Epirubicin
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Cyclophosphamide
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Fluorouracil
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multidrug resistance-associated protein 1