Proteins breast cancer resistance

The breast cancer resistance protein (BCRP) belongs to the G-branch of the ABC-transporter family (ABCG2). In contrast to most other ABC-proteins, BCRP consists of only one transmembrane domain (TDM) with one nucleotide binding fold (NBF) at its C-terminus. Because of this structural characteristic BCRP as well as other ABC-transporters with only one TMD are termed half transporters. To achieve functional activity these transporters have to form hetero- or homodimers. BCRP is involved in the multidrug resistance of certain tumors and transports endogenous compounds like cholesterol and steroid hormones. 

Both influx and efflux transporters are located in intestinal epithelial cells and can either increase or decrease oral absorption. Influx transporters such as human peptide transporter 1 (hPEPTl), apical sodium bile acid transporter (ASBT), and nucleoside transporters actively transport drugs that mimic their native substrates across the epithelial cell, whereas efflux transporters such as P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), and breast cancer resistance protein (BCRP) actively pump absorbed drugs back into the intestinal lumen. 

Breast cancer resistance protein (BCRP) is another ATP-dependent efflux transporter that confers resistance to a variety of anticancer agents, including... 

Mao Q and Unadkat JD. Role of the breast cancer resistance protein (ABCG2) in drug transport. AAPS J 2005 7 E118-33. 

Zhang S, Yang X, Coburn RA and Morris ME. Structure activity relationships and quantitative structure activity relationships for the flavonoid-mediated inhibition of breast cancer resistance protein. Biochem Pharmacol 2005 70 627-39. 

Brinkhuis, R. F., Maliepaard, M., Beijnen, J. H. et al., Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan, J. Natl. Cancer Inst. 2000, 92, 1651-1656. 

Biliary Excretion Mediated by Breast Cancer-Resistant Protein (BCRP)... 

Breast Cancer Resistance Protein (BCRP, also known as MXR or ABCP), first cloned from mitoxantrone and anthracycline-resistant breast and colon cancer cells [188, 189] is a half-transporter efflux pump believed to function as a homo-or hetero-dimer. Following its identification, BCRP-mediated drug resistance was observed for topoisomerase inhibitors including camptothecins [190, 191] and in-dolocarbazoles [192]. In normal tissues, BCRP was detected in placental syncytio-trophoblasts, hepatocyte canalicular membrane, apical intestinal epithelia and vascular endothelial cells [193]. These findings support the important role BCRP plays in modulating topotecan bioavailability, fetal exposure and hepatic elimination [194]. Considering that the substrates and tissue distributions for BCRP overlap somewhat with MDR1 and MRPs [195], additional studies will be required to define the relative contribution of each of these transporters in the overall and tis-... 

Komatani H, Kotani H, Hara Y, Naka-gawa R, Matsumoto M, Arakawa H et al. Identification of breast cancer resistant protein/mitoxantrone resistance/pla-centa-specific, ATP-binding cassette transporter as a transporter of NB-506 and J-107088, topoisomerase I inhibitors with an indolocarbazole stmcture. Cancer Res 2001 61(7) 2827-2832. 

Maliepaard M, Scheffer GL, Faneyte IF, van Gastelen MA, Pijnenborg AC, Schinkel AH et al. Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer Res 2001 61(8)3458-3464. 

Kruijtzer, C.M., Beijnen, J.H., Rosing, H., ten Bokkel Huinink, W.W., Schot, M., Jewell, R.C., Paul, E.M. and Schellens, J. H. (2002) Increased oral bioavailability of topotecan in combination with the breast cancer resistance protein and P-glycoprotein inhibitor GF120918. Journal of Clinical Oncology, 20, 2943-2950. 

BCRP Breast cancer resistance protein CYP Cytochrome P450... 

Allen JD, Schinkel AH (2002) Multidmg resistance and pharmacological protection mediated by the breast cancer resistance protein (BCRP/ABCG2). Mol Cancer Ther 1 427-434. 

Merino G, Alvarez Al, Pulido MM, Molina AJ, Schinkel AH, Prieto JG (2006) Breast cancer resistance protein (BCRP/ABCG2) transports fluoroquinolone... 

Breast Cancer Resistance Protein (BCRP/ABCG2)... 

In contrast to P-gp and the MRP proteins, the breast cancer resistance protein (BCRP) contains six transmembrane domains and only one ATP-binding domain. It was first cloned from the breast cancer cell line MCF-7 selected in doxombicin, in the presence of the P-gp inhibitor verapamil. It is found in many human tissues, such as the placenta, small intestine, colon, and liver [133], It is localized to the apical membrane of epithelial cells of the small intestine and colon and to the bile canalicular membrane in the liver and is involved in reducing intestinal uptake, increasing hepatobiliary excretion, etc., leading to diminished oral bioavailability. cDNA sequences identical to BCRP and named MXR and ABCP, respectively, were independently isolated from human colon carcinoma cells and human placenta [134], BCRP requires... 

X. Wang and M. Baba. The role of breast cancer resistance protein (BCRP/ ABCG2) in cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors. Antivir Chem Chemother. 16 213-216 (2005). 

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