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


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.


CONCLUSIONS
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.
Faneyte
Ian F
IF
Department of Experimental Therapy, Cancer Institute / Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. m.vd.vijver@nki.nl
Kristel
Petra M P
PM
van de Vijver
Marc J
MJ
D018943:Anthracyclines / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D045744:Cell Line, Tumor; D017322:Clinical Trials, Phase II as Topic; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D015251:Epirubicin / Q000008:administration & dosage; D005472:Fluorouracil / Q000008:administration & dosage; D015870:Gene Expression / Q000187:drug effects; D019450:Genes, MDR / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D020360:Neoadjuvant Therapy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D018943:Anthracyclines; D003520:Cyclophosphamide; D015251:Epirubicin; D005472:Fluorouracil; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; C000715087:ABCC2 protein, human; C114462:multidrug resistance-associated protein 3; C421109:multidrug resistance-associated protein 1