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<i>-</i>transporter protein that acts as an energy<i>-</i>dependent efflux pump and may be associated with the multidrug<i>-</i>resistant phenotype. The aim of this study was to determine the association between BCRP expression and 5<i>-</i>fluorouracil (5<i>-</i>FU) resistance in clinical breast cancer tissue specimens. The BCRP expression was investigated using quantitative reverse<i>-</i>transcriptase polymerase chain reaction (RT<i>-</i>PCR) by use of the Master SYBR-Green I reagent and immunohistochemistry (IHC) by use of the BXP<i>-</i>21 anti<i>-</i>BCRP monoclonal antibody in clinical breast cancer tissue specimens. Chemosensitivity to 5<i>-</i>FU for BCRP<i>-</i>positive clinical breast cancer tissue specimens was colorimetrically assessed with the cytotoxicity assay through methyl thiazolyl tetrazolium (MTT) reduction. A total of 37 BCRP<i>-</i>positive clinical breast cancer tissue specimens were identified with quantitative RT<i>-</i>PCR and IHC. There was a significant correlation in BCRP expression between the results of quantitative RT<i>-</i>PCR and IHC in the specimens. The fold resistance to 5<i>-</i>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<i>-</i>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<i>-</i>positive specimens.