Expression of the breast cancer resistance protein and 5-fluorouracil resistance in clinical breast cancer tissue specimens

Abstract

The breast cancer resistance protein (BCRP) is a recently characterized xenobiotic half-transporter protein that acts as an energy-dependent efflux pump and may be associated with the multidrug-resistant phenotype. The aim of this study was to determine the association between BCRP expression and 5-fluorouracil (5-FU) resistance in clinical breast cancer tissue specimens. The BCRP expression was investigated using quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) by use of the Master SYBR-Green I reagent and immunohistochemistry (IHC) by use of the BXP-21 anti-BCRP monoclonal antibody in clinical breast cancer tissue specimens. Chemosensitivity to 5-FU for BCRP-positive clinical breast cancer tissue specimens was colorimetrically assessed with the cytotoxicity assay through methyl thiazolyl tetrazolium (MTT) reduction. A total of 37 BCRP-positive clinical breast cancer tissue specimens were identified with quantitative RT-PCR and IHC. There was a significant correlation in BCRP expression between the results of quantitative RT-PCR and IHC in the specimens. The fold resistance to 5-FU was 7–12 compared to sensitivity to paclitaxel as determined by the colorimetric assay through MTT reduction in the 37 specimens. Our study results indicated that 5-FU resistance may be mediated by BCRP expression in clinical breast cancer tissue specimens, which may help optimize the design of breast cancer clinical chemotherapy schemes in BCRP-positive specimens.