A new multidrug resistance protein at the blood–brain barrier

Eisenblätter, Tanja; Galla, Hans‐Joachim

doi:10.1016/s0006-291x(02)00376-5

Cited by 141 publications

(82 citation statements)

References 13 publications

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“…Phenytoin and carbamazepine also induced Bcrp1 levels significantly in the liver. While dexamethasone was not found to induce Bcrp1, a second study, using a cDNA subtraction technique to compare gene expression in untreated versus hydrocortisonetreated porcine endothelial cells, demonstrated overexpression of porcine BCRP after hydrocortisone (Eisenblatter and Galla, 2002). Elevated basal expression of BCRP, Pgp, and MRP1 were noted in thermoresistant human gastric carcinoma EPG85-257 cells, suggesting the possibility that cellular responses to heat may induce the expression of these transporters .…”

Section: Organization Of the Bcrp Gene And Promotermentioning

confidence: 94%

“…The porcine homologue of BCRP was found in cultured brain capillary endothelial cells, which have high transendothelial electrical resistances and low cell monolayer permeabilities for small solutes very similar to the blood-brain barrier (Eisenblatter and Galla, 2002). Further analysis revealed that the porcine BCRP was expressed in brain tissue in vivo and was predominantly localized within the endothelial cells isolated from brain capillaries.…”

Section: Expression Of Bcrp In Normal Tissuesmentioning

confidence: 99%

“…A 656 amino-acid ABC transporter that is 85% identical and 90% homologous to human BCRP was recently isolated from porcine brain capillary endothelial cells (Eisenblatter and Galla, 2002). Termed the brain multidrug resistance protein (BMDP), the protein is expressed in brain tissue in vivo, predominantly within the brain capillary endothelial cells.…”

Section: Murine and Porcine Orthologues Of Bcrpmentioning

confidence: 99%

“…The expression of porcine BCRP was induced in brain capillary endothelial cells by hydrocortisone (Eisenblatter and Galla, 2002), suggesting that this steroid may be a substrate for the transporter. Estrone and 17b-estradiol have been found to potentiate the cytotoxicity of SN-38, mitoxantrone, and topotecan in BCRP-transfected cells but not in a parental K562 line (Imai et al, 2002b).…”

Section: Expression Of Bcrp In Normal Tissuesmentioning

confidence: 99%

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Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2)

2003

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Observations of functional adenosine triphosphate (ATP)-dependent drug efflux in certain multidrug-resistant cancer cell lines without overexpression of P-glycoprotein or multidrug resistance protein (MRP) family members suggested the existence of another ATP-binding cassette (ABC) transporter capable of causing cancer drug resistance. In one such cell line (MCF-7/AdrVp), the overexpression of a novel member of the G subfamily of ABC transporters was found. The new transporter was termed the breast cancer resistance protein (BCRP), because of its identification in MCF-7 human breast carcinoma cells. BCRP is a 655 amino-acid polypeptide, formally designated as ABCG2. Like all members of the ABC G (white) subfamily, BCRP is a half transporter. Transfection and enforced overexpression of BCRP in drug-sensitive MCF-7 or MDA-MB-231 cells recapitulates the drug-resistance phenotype of MCF-7/AdrVp cells, consistent with current evidence suggesting that functional BCRP is a homodimer. BCRP maps to chromosome 4q22, downstream from a TATA-less promoter. The spectrum of anticancer drugs effluxed by BCRP includes mitoxantrone, camptothecin-derived and indolocarbazole topoisomerase I inhibitors, methotrexate, flavopiridol, and quinazoline ErbB1 inhibitors. Transport of anthracyclines is variable and appears to depend on the presence of a BCRP mutation at codon 482. Potent and specific inhibitors of BCRP are now being developed, opening the door to clinical applications of BCRP inhibition. Owing to tissue localization in the placenta, bile canaliculi, colon, small bowel, and brain microvessel endothelium, BCRP may play a role in protecting the organism from potentially harmful xenobiotics. BCRP expression has also been demonstrated in pluripotential 'side population' stem cells, responsible for the characteristic ability of these cells to exclude Hoechst 33342 dye, and possibly for the maintenance of the stem cell phenotype. Studies are emerging on the role of BCRP expression in drug resistance in clinical cancers. More prospective studies are needed, preferably combining BCRP protein or mRNA quantification with functional assays, in order to determine the contribution of BCRP to drug resistance in human cancers.

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Section: Organization Of the Bcrp Gene And Promotermentioning

confidence: 94%

Section: Expression Of Bcrp In Normal Tissuesmentioning

confidence: 99%

Section: Murine and Porcine Orthologues Of Bcrpmentioning

confidence: 99%

Section: Expression Of Bcrp In Normal Tissuesmentioning

confidence: 99%

See 2 more Smart Citations

Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2)

2003

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“…In addition to the well-recognized role of P-gp and Mrp2, BCRP is an important efflux transporter that restricts the entrance of certain substances into brain [17][18][19] . Several studies have demonstrated that the function and expression of BCRP at the BBB are markedly altered under various disease states, including diabetes mellitus [20] , primary CNS lymphoma [21] and glioblastoma [22] .…”

Section: Introductionmentioning

confidence: 99%

Unconjugated bilirubin elevation impairs the function and expression of breast cancer resistance protein (BCRP) at the blood-brain barrier in bile duct-ligated rats

Ling

Zhang

et al. 2016

Acta Pharmacol Sin

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Aim: Liver failure is associated with dyshomeostasis of efflux transporters at the blood-brain barrier (BBB), which contributes to hepatic encephalopathy. In this study we examined whether breast cancer resistance protein (BCRP), a major efflux transporter at the BBB, was altered during liver failure in rats. Methods: Rats underwent bile duct ligation (BDL) surgery, and then were sacrificed after intravenous injection of prazosin on d3, d7 and d14. The brains and blood samples were collected. BCRP function at the BBB was assessed by the brain-to-plasma prazosin concentration ratio; Evans Blue extravasation in the brain tissues was used as an indicator of BBB integrity. The protein levels of BCRP in the brain tissues were detected. Human cerebral microvessel endothelial cells (HCMEC/D3) and Madin-Darby canine kidney cells expressing human BCRP (MDCK-BCRP) were tested in vitro. In addition, hyperbilirubinemia (HB) was induced in rats by intravenous injection of unconjugated bilirubin (UCB). Results: BDL rats exhibited progressive decline of liver function and HB from d3 to d14. In the brain tissues of BDL rats, both the function and protein levels of BCRP were progressively decreased, whereas the BBB integrity was intact. Furthermore, BDL rat serum significantly decreased BCRP function and protein levels in HCMEC/D3 cells. Among the abnormally altered components in BDL rat serum tested, UCB (10, 25 µmol/L) dose-dependently inhibit BCRP function and protein levels in HCMEC/D3 cells, whereas 3 bile acids (CDCA, UDCA and DCA) had no effect. Similar results were obtained in MDCK-BCRP cells and in the brains of HB rats. Correlation analysis revealed that UCB levels were negatively correlated with BCRP expression in the brain tissues of BDL rats and HB rats as well as in two types of cells tested in vitro. Conclusion: UCB elevation in BDL rats impairs the function and expression of BCRP at the BBB, thus contributing to hepatic encephalopathy.

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ABC Superfamily Transporters at the Human Blood–Brain Barrier

Scherrmann

2009

ABC Transporters and Multidrug Resistance

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A new multidrug resistance protein at the blood–brain barrier

Cited by 141 publications

References 13 publications

Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2)

Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2)

Unconjugated bilirubin elevation impairs the function and expression of breast cancer resistance protein (BCRP) at the blood-brain barrier in bile duct-ligated rats

ABC Superfamily Transporters at the Human Blood–Brain Barrier

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