ABCMdb

ABCG2 p.Arg482Met

[switch to full view]
Comments [show]

None has been submitted yet.

Publications

PMID: 11956086 [PubMed] Allen JD et al: "A mutation hot spot in the Bcrp1 (Abcg2) multidrug transporter in mouse cell lines selected for Doxorubicin resistance."

No. Sentence Comment

146 Clearly, the mouse Bcrp1 R482M and R482S mutants confer enhanced resistance to anthracyclines compared with the wild-type transporter. Login to comment
149 Resistance to topotecan was at least 10-fold lower, relative to the anthracyclines and bisantrene, in the 88.6-derived R482M and R482S mutant lines, as was found for the human R482G mutant (13). Login to comment
150 In this context it is also noteworthy that cell lines carrying either the R482M or R482S Bcrp1 mutants showed greatly reduced (and Ko143-reversible) accumulation of the dye rhodamine 123 (Fig. 3C), as was observed previously for the R482G and R482T mutants of human BCRP (13). Login to comment
144 Clearly, the mouse Bcrp1 R482M and R482S mutants confer enhanced resistance to anthracyclines compared with the wild-type transporter. Login to comment
147 Resistance to topotecan was at least 10-fold lower, relative to the anthracyclines and bisantrene, in the 88.6-derived R482M and R482S mutant lines, as was found for the human R482G mutant (13). Login to comment
148 In this context it is also noteworthy that cell lines carrying either the R482M or R482S Bcrp1 mutants showed greatly reduced (and Ko143-reversible) accumulation of the dye rhodamine 123 (Fig. 3C), as was observed previously for the R482G and R482T mutants of human BCRP (13). Login to comment

PMID: 12208758 [PubMed] Volk EL et al: "Overexpression of wild-type breast cancer resistance protein mediates methotrexate resistance."

No. Sentence Comment

154 Similar results were also seen in murine Bcrp1 R482M and R482S mutants (32). Login to comment
153 Similar results were also seen in murine Bcrp1 R482M and R482S mutants (32). Login to comment

PMID: 12374800 [PubMed] Ozvegy C et al: "Characterization of drug transport, ATP hydrolysis, and nucleotide trapping by the human ABCG2 multidrug transporter. Modulation of substrate specificity by a point mutation."

No. Sentence Comment

23 Interestingly, in some drug-selected mouse cell lines, mutation of the equipositional amino acid in mouse ABCG2 occurred, causing altered drug resistance profiles for the mutant variants R482S and R482M (21). Login to comment

PMID: 12488537 [PubMed] Wang X et al: "Breast cancer resistance protein (BCRP/ABCG2) induces cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors."

No. Sentence Comment

194 Our preliminary analysis for the full-length BCRP cDNA identified the R482M mutation in MT-4/DOX500 cells (data not shown). Login to comment

PMID: 14566825 [PubMed] Miwa M et al: "Single amino acid substitutions in the transmembrane domains of breast cancer resistance protein (BCRP) alter cross resistance patterns in transfectants."

No. Sentence Comment

13 A doxorubicin-resistant human breast cancer cell line MCF-7 AdVp3000 and a mitoxantrone-resistant human colon carcinoma cell line S1-M1-80 expressed R482T- and R482G-BCRP, respectively and showed high resistance to mitoxantrone and doxorubicin.5,6,13 Doxorubicin-resistant murine fibroblast cell lines also expressed R482M- or R482S-BCRP and showed high resistance to mitoxantrone and doxorubicin.14 We recently identified the substitution R482M in a doxorubicin-resistant human T cell line MT-4/DOX500.23 We made 32 mutant BCRP cDNAs with an amino acid substitution in the TMs and examined the effect of the substitutions on cellular drug resistance. Login to comment
64 PA/R482N, PA/R482C, PA/R482M, PA/R482S, PA/R482T, PA/R482V, PA/R482A, PA/R482G, PA/R482E PA/R482W and PA/R482D (Group 2) showed higher degrees of resistance to mitoxantrone than to SN-38. Login to comment
135 MCF-7 AdVp3000 established by treating MCF-7 cells with 3 ␮g/ml of doxorubicin and 5 ␮g/ml of verapamil overexpressed R482T-BCRP.5,13 S1-M1-80 established by treating human colon carcinoma S1 cells with 80 ␮M mitoxantrone overexpressed R482G-BCRP.6,13 These resistant cells exhibited high resistance to doxorubicin and mitoxantrone.5,6,13 We found recently that MT-4/DOX500 cells established by treating human T cell MT-4 cells with 500 ng/ml of doxorubicin overexpressed R482M-BCRP.23 Two doxorubicin-resistant murine fibroblast lines 88.6/D800-A and 88.6/D800-B overexpressed R482M-BCRP and R482S-BCRP, respectively.14 Another doxorubicin-resistant cell line KOT52/D800 from mouse fibroblasts co-expressed wild-type BCRP and R482M-BCRP.14 In addition to anthracyclines and mitoxantrone, cells transfected with R482-mutant BCRP cDNAs also showed high resistance to methotrexate.28 Theoretically, 9 FIGURE 6 - Accumulation of [3 H]mitoxantrone in R482-mutant BCRP transfectants. PA/WT2, PA/R482G and PA/R482S were mixed populations of the transfected cells established after the 2-step selection with 120 ng/ml methotrexate and 1 ng/ml mitoxantrone. Login to comment
147 Cells transfected with R482G- (GGG), R482M- (ATG), R482T- (ACG), or R482S- (AGT and AGC) BCRP cDNA showed greater resistance to mitoxantrone and doxorubicin than PA/WT2 (Fig. 2). Login to comment
148 As described above, human drug-resistant cell lines MCF-7 AdVp3000, S1-M1-80, MT-4/DOX500 and a mouse drug-resistant line 88.6/D800-B overexpressed R482T- (ACG), R482G- (GGG), R482M- (ATG) and R482S- (AGT) BCRP, respectively.5,6,13,14,23 The other possible mutations are R482W (TGG) and R482K (AAG). Login to comment
149 PA317 cells expressing R482W- BCRP (PA/R482W) showed somewhat higher levels of resistance to mitoxantrone and doxorubicin than PA/WT2, but the resistance levels were lower than those in PA/ R482G, PA/R482M, PA/R482T and PA/R482S. Login to comment
163 Group 2 members (PA/R482N, PA/R482C, PA/R482M, PA/R482S, PA/R482T, PA/R482V, PA/ R482A, PA/R482G, PA/R482E PA/R482W and PA/R482D) showed higher degrees of resistance to mitoxantrone than to SN-38. Login to comment

PMID: 14612912 [PubMed] Robey RW et al: "Mutations at amino-acid 482 in the ABCG2 gene affect substrate and antagonist specificity."

No. Sentence Comment

133 Mutations at amino-acid 482 have included R482G and R482T in human cancer cells; R482S and R482M in mouse fibroblast lines (Honjo et al, 2001; Allen et al, 2002); and a recently reported R482M mutation in a doxorubicin-selected human T-cell line (Wang et al, 2003). Login to comment
152 The findings presented here parallel those of Allen et al, (2002), who described two mutations, R482M and R482S, in mouse fibroblast cells lacking functional Mdr1, Mdr2, and Mrp1. Login to comment

PMID: 14754410 [PubMed] Han B et al: "Multidrug resistance in cancer chemotherapy and xenobiotic protection mediated by the half ATP-binding cassette transporter ABCG2."

No. Sentence Comment

106 However, no polymorphism at amino acid 482 was identified to correspond to the Arg482 Gly, Arg482 Met, or Arg482 Thr mutation that has been identified in drug selected cell lines. Login to comment

PMID: 15165903 [PubMed] Sarkadi B et al: "ABCG2 -- a transporter for all seasons."

No. Sentence Comment

119 The mutants having R482G or R482T (R482M or R482S in the mouse abcg2) showed altered substrate specificity as compared to the wild-type protein, i.e., they conferred increased mitoxantrone or doxorubicin (DOX) resistance and rhodamine 123 transport capacity (see Fig. 2, [42,43]). Login to comment

PMID: 15345326 [PubMed] Wang X et al: "Induction of cellular resistance to nucleoside reverse transcriptase inhibitors by the wild-type breast cancer resistance protein."

No. Sentence Comment

2 However, this BCRP was found to have a mutation of Arg to Met at position 482 (BCRPR482M). Login to comment
32 This BCRP was found to have a mutation of Arg to Met at position 482 (BCRPR482M). Login to comment

PMID: 15670731 [PubMed] Ozvegy-Laczka C et al: "Single amino acid (482) variants of the ABCG2 multidrug transporter: major differences in transport capacity and substrate recognition."

No. Sentence Comment

29 The mutants, containing R482G, T or M (R482M or S in the mouse abcg2), showed altered substrate specificity [22-24]. Login to comment
48 The two internal complementary primer pairs containing the specific mutation were: 5V-tta tta cca atg atc atg tta cc-3Vand 5-Vgg taa cat gat cat tgg taa taa-3V (R482I), 5V-tta tca gat cta tta ccc atg-3Vand 5V-gg taa cat cat cat ggg taa t-3V(R482M), 5V-ta ccc atg tcg atg tta cca a-3Vand 5V-t tgg taa cat cga cat ggg ta-3V(R482S), 5V-cc atg gac atg tta cca tcg att ata-3V and 5V-tat aat cga tgg taa cat gtc cat gg-3V (R482D), 5V-atg tta cca tcg att ata ttt acc-3Vand 5V-cc atg aat atg tta cca tcg att ata-3V (R482N), 5V-tta tta cct atg aag atg tta-3V cc and 5V-gg taa cat ctt cat agg taa taa-3V(R482K) and 5V-tta tta cct atg tac atg tta cc-3Vand 5V-gg taa cat gta cat agg taa taa-3V (R482Y). Login to comment

PMID: 15838659 [PubMed] Morisaki K et al: "Single nucleotide polymorphisms modify the transporter activity of ABCG2."

No. Sentence Comment

25 Wang et al. have also identified an R482M mutation in a doxorubicin-resistant human T-cell line [47]. Login to comment

PMID: 16158227 [PubMed] Krishnamurthy P et al: "The ABC transporter Abcg2/Bcrp: role in hypoxia mediated survival."

No. Sentence Comment

115 The mutants having R482G or R482T (R482M or R482S in the mouse Bcrp) showed altered transport properties as compared to the wild-type protein (Honjo et al. 2001; Allen et al. 2002). Login to comment

PMID: 16166320 [PubMed] Shafran A et al: "ABCG2 harboring the Gly482 mutation confers high-level resistance to various hydrophilic antifolates."

No. Sentence Comment

22 Sequencing of the Abcg2 gene in these drug-resistant cell lines identified two mutations, R482M and R482S. Login to comment

PMID: 16337740 [PubMed] Cervenak J et al: "The role of the human ABCG2 multidrug transporter and its variants in cancer therapy and toxicology."

No. Sentence Comment

80 The cDNA sequence analysis of the MCF-7/AdVP3000 human breast cancer cell line and the S1M1-80 human colon cancer cell line revealed that in these cell lines, each showing anthracycline resistance and an ability to extrude rhodamine 123, a single amino acid change occurred at position 482, resulting an R482T (c.1445GOC) mutant in the MCF-7/AdVP3000 cell line, an R482G replacement (c.1444AOG) in S1M1-80 cells, and an R482M substitution (c.1445GOT) in the MT-4/DOX500 human T cell line [27,41,54]. Login to comment
81 Moreover, in the 88.6/D800-A, 88.6/D800-B and KOT52/ D800 mouse fibroblast cell lines, an R482M (KOT52/D800 and 88.6/D800-A cells) and an R482S (88.6/D800-B cells) mutation was observed, with a similar, anthracycline resistant phenotype [42]. Login to comment

PMID: 16815914 [PubMed] Ejendal KF et al: "The nature of amino acid 482 of human ABCG2 affects substrate transport and ATP hydrolysis but not substrate binding."

No. Sentence Comment

30 Recently, another ABCG2 variant was found to have a mutation of arginine to methionine at position 482 in a doxorubicin-resistant CD4+ T-cell line (Wang et al. 2003). Login to comment

PMID: 17015488 [PubMed] Sarkadi B et al: "Human multidrug resistance ABCB and ABCG transporters: participation in a chemoimmunity defense system."

No. Sentence Comment

804 Interestingly, the same phenomenon was observed in the case of the mouse Abcg2 protein; drug selection induced a mutation exactly at the same position (R482M or R482S in the mouse Abcg2), similarly altering the substrate handling of this ortholog (5). Login to comment

PMID: 22115866 [PubMed] Telbisz A et al: "Antibody binding shift assay for rapid screening of drug interactions with the human ABCG2 multidrug transporter."

No. Sentence Comment

18 The mutants, containing R482G, T (or R482M or S in the mouse Abcg2), showed altered substrate specificities. Login to comment