Breast cancer resistance protein (BCRP/ABCG2): its role in multidrug resistance and regulation of its gene expression.
Article Details
- CitationCopy to clipboard
Nakanishi T, Ross DD
Breast cancer resistance protein (BCRP/ABCG2): its role in multidrug resistance and regulation of its gene expression.
Chin J Cancer. 2012 Feb;31(2):73-99. doi: 10.5732/cjc.011.10320. Epub 2011 Nov 18.
- PubMed ID
- 22098950 [ View in PubMed]
- Abstract
Breast cancer resistance protein (BCRP)/ATP-binding cassette subfamily G member 2 (ABCG2) is an ATP-binding cassette (ABC) transporter identified as a molecular cause of multidrug resistance (MDR) in diverse cancer cells. BCRP physiologically functions as a part of a self-defense mechanism for the organism; it enhances elimination of toxic xenobiotic substances and harmful agents in the gut and biliary tract, as well as through the blood-brain, placental, and possibly blood-testis barriers. BCRP recognizes and transports numerous anticancer drugs including conventional chemotherapeutic and targeted small therapeutic molecules relatively new in clinical use. Thus, BCRP expression in cancer cells directly causes MDR by active efflux of anticancer drugs. Because BCRP is also known to be a stem cell marker, its expression in cancer cells could be a manifestation of metabolic and signaling pathways that confer multiple mechanisms of drug resistance, self-renewal (stemness), and invasiveness (aggressiveness), and thereby impart a poor prognosis. Therefore, blocking BCRP-mediated active efflux may provide a therapeutic benefit for cancers. Delineating the precise molecular mechanisms for BCRP gene expression may lead to identification of a novel molecular target to modulate BCRP-mediated MDR. Current evidence suggests that BCRP gene transcription is regulated by a number of trans-acting elements including hypoxia inducible factor 1alpha, estrogen receptor, and peroxisome proliferator-activated receptor. Furthermore, alternative promoter usage, demethylation of the BCRP promoter, and histone modification are likely associated with drug-induced BCRP overexpression in cancer cells. Finally, PI3K/AKT signaling may play a critical role in modulating BCRP function under a variety of conditions. These biological events seem involved in a complicated manner. Untangling the events would be an essential first step to developing a method to modulate BCRP function to aid patients with cancer. This review will present a synopsis of the impact of BCRP-mediated MDR in cancer cells, and the molecular mechanisms of acquired MDR currently postulated in a variety of human cancers.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Docetaxel ATP-binding cassette sub-family G member 2 Protein Humans UnknownSubstrateDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAbemaciclibSulfasalazine Sulfasalazine may decrease the excretion rate of Abemaciclib which could result in a higher serum level. AbemaciclibNovobiocin Novobiocin may decrease the excretion rate of Abemaciclib which could result in a higher serum level. AbemaciclibHesperetin Hesperetin may decrease the excretion rate of Abemaciclib which could result in a higher serum level. AbemaciclibDaidzin Daidzin may decrease the excretion rate of Abemaciclib which could result in a higher serum level. AbemaciclibNaringenin Naringenin may decrease the excretion rate of Abemaciclib which could result in a higher serum level.