ABCG2

ABC Transporters. Figure 1 Structure of ABCB 1, ABCC1, and ABCG2 (NBF nucleotide binding fold TMD transmembrane domaine. Modified according to www.iwaki-kk.co.jp/bio/specialedition/se02.htm). 

BCRP (ABCG2) Cisplatin, folate, methotrexate, mitoxantrone, topotecan, irinotecan, steroids (cholesterol, testosterone, progesterone), certain chlorophyll metabolites, and others... 

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. 

Although in vitro models clearly show that MDR transporters can protect tumor cells, their relevance in clinical oncology remains controver sial. As is the case for most potentially useful cancer biomarkers, no universally embraced guidelines for analytical or clinical validation of MDR transporters exist. Evidence linking ABCB1 Pgp/MDRl expression with poor clinical outcome is most conclusive for breast cancer, sarcoma, and certain types of leukemia. The relevance of the other MDR transporters in clinical MDR is still unclear. The prognostic implication of ABCCl/ MRPl remains controversial and very little is known clinically about ABCG2. 

Krishnamurthy P, Schuetz JD (2006) Role of ABCG2/ BCRP in biology and medicine. Annu Rev Pharmacol Toxicol 46 381-410... 

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

Chearwae, W. et al.. Modulation of the function of the multidrug resistance-linked ATP-binding transporter ABCG2 by the cancer chemopreventive agent curcumin. Mol. Cancer Then, 5, 1995, 2006. 

Limtraknl, P. et al.. Modulation of the function of three ABC drug transporters, P-glycoprotein (ABCBl), mitoxantrone resistance protein (ABCG2) and multidrug resistance protein 1 (ABCCl) by tetrahydroenrenmin, a major metabolite of cur-enmin. Mol. Cell Biochem., 296, 85, 2007. 

Fetsch P, Abati A, Ross DD et al. The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2). J Cell Sci 2000 113(Pt 11) 2011-2021. 

For other efflux transporters such as BCRP (ABCG2), human pharmacokinetic and pharmacodynamic data are currently rare. However, an investigation of the influence of polymorphisms in ABC-transporter genes on the accumulation of nelfinavir in peripheral blood mononuclear cells (PBMCs) revealed no associations between the polymorphisms in the transporters analyzed and the accumulation of nelfinavir in the PBMCs [151], A second study in patients clearly demonstrated an increase in the AUC of the orally and intravenously administered BCRP substrate topotecan when it is given with GF120918, an inhibitor of P-glycoprotein and BCRP [152],... 

T. (2006) A new strategy of high-speed screening and quantitative structure-activity relationship analysis to evaluate human ATP-binding cassette transporter ABCG2-drug interactions. Journal of Pharmacology... 

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)... 

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). 

M. Ceckova, A. Libra, P. Pavek, P. Nachtigal, M. Brabec, R. Fuchs, and F. Staud. Expression and functional activity of breast cancer resistance protein (BCRP, ABCG2) transporter in the human choriocarcinoma cell line BeWo. Clin Exp Pharmacol Physiol. 33 58-65 (2006). 

B. Sarkadi, C. Ozvegy-Laczka, K. Nemet, and A. Varadi. ABCG2—a transporter for all seasons. FEBS Lett. 567 116-120 (2004). 

K. Shiozawa, M. Oka, H. Soda, M. Yoshikawa, Y. Ikegami, J. Tsurutani, K. Nakatomi, Y. Nakamura, S. Doi, T. Kitazaki, Y. Mizuta, K. Murase, H. Yoshida, D.D. Ross, and S. Kohno. Reversal of breast cancer resistance protein (BCRP/ABCG2)-mediated drug resistance by novobiocin, a coumermycin antibiotic. Int J Cancer. 108 146-151 (2003). 

S. Zhang, X. Yang, and M.E. Morris. Flavonoids are inhibitors of breast cancer resistance protein (ABCG2)-mediated transport. Mol Pharmacol. 65 1208-1216... 

T. Janvilisri, H. Venter, S. Shahi, G. Reuter, L. Balakrishnan, and H.W. Van Veen. Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 278 20645-20651 (2003). 

Y. Imai, E. Ishikawa, S. Asada, and Y. Sugimoto. Estrogen-mediated post-transcriptional down-regulation of breast cancer resistance protein/ABCG2. Cancer Res. 65 596-604 (2005). 

S. Yasuda, S. Itagaki, T. Hirano, and K. Iseki. Effects of sex hormones on regulation of ABCG2 expression in the placental cell line BeWo. J Pharm Pharm Sci. 9 133-139 (2006). 

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