Article

A multidrug transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci USA

Greenebaum Cancer Center of the University of Maryland, Baltimore MD 21201, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 01/1999; 95(26):15665-70. DOI: 10.1073/pnas.95.26.15665
Source: PubMed

ABSTRACT

MCF-7/AdrVp is a multidrug-resistant human breast cancer subline that displays an ATP-dependent reduction in the intracellular accumulation of anthracycline anticancer drugs in the absence of overexpression of known multidrug resistance transporters such as P glycoprotein or the multidrug resistance protein. RNA fingerprinting led to the identification of a 2.4-kb mRNA that is overexpressed in MCF-7/AdrVp cells relative to parental MCF-7 cells. The mRNA encodes a 655-aa [corrected] member of the ATP-binding cassette superfamily of transporters that we term breast cancer resistance protein (BCRP). Enforced expression of the full-length BCRP cDNA in MCF-7 breast cancer cells confers resistance to mitoxantrone, doxorubicin, and daunorubicin, reduces daunorubicin accumulation and retention, and causes an ATP-dependent enhancement of the efflux of rhodamine 123 in the cloned transfected cells. BCRP is a xenobiotic transporter that appears to play a major role in the multidrug resistance phenotype of MCF-7/AdrVp human breast cancer cells.

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    • "yle et al . , 1998 ) . BCRP is a half - transporter member of the ABCG subfamily ( ABCG2 ) with a size of 72 kDa . BCRP probably functions as a homodimer . The expression of BCRP overlaps largely with that of P - gp , because the protein can be found in tissues such as the placenta , prostate , small intestine , brain , colon , liver , and ovary ( Doyle et al . , 1998 ) . Overexpression of BCRP is associated with resistance to a wide range of different anticancer agents : anthracyclines , mitoxantrone , flavopiridol , camptothecins , and antifolates ( Assaraf , 2006 ; Bihorel et al . , 2007 ; Robey et al . , 2007 ) . FIGURE 2 | Key HBMC correlations of compound 1 ."
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    • "ATP-binding cassette (ABC) transporters, which transport a variety of molecules including chemotherapeutic drugs, are known to mediate the multidrug resistance of BC [4] [5] [6]. ABCG2 protein, also called breast cancer resistance protein (BCRP), belongs to the family of ABC transporters, mediating high levels of resistance to a variety of anticancer agents [7] [8] [9]. "
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    • "Many intrinsic and acquired properties such as overexpression of anti-apoptotic proteins, drug efflux transporters , and detoxifying enzymes make CSCs resistant to anticancer drugs [16]. ATP-binding cassette sub-family G member 2 (ABCG2) is a major multidrug resistance pump that renders cancer cells resistant to chemotherapeutic drugs [17], which is a downstream target of sonic hedgehog (SHH)-glioma-associated oncogene homolog (GLI) pathway [18]. SHH signal is critical for the tumorigenesis of primary gastric CSCs that is mediated through Patched 1 (PTCH1) and smoothened (SMO) receptors, where the absence or presence of HH ligands controls the PTCH1 and SMO activities [19]. "
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