Human Breast Cancer Resistance Protein: Interactions with Steroid Drugs, Hormones, the Dietary Carcinogen 2-Amino-1-methyl-6-phenylimidazo(4,5-<i>b</i>)pyridine, and Transport of Cimetidine

Pávek, Petr; Merino, Gracia; Wagenaar, Els; Bolscher, Ellen; Novotná, Martina; Jonker, Johan W.; Schinkel, Alfred H.

doi:10.1124/jpet.104.073916

Cited by 256 publications

(203 citation statements)

References 26 publications

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“…The ratio of these same drug transporters is also important for MTX pharmacodynamics in paediatric ALL (Kager et al, 2005). ABCG2 is a major transporter for MTX that can be directly inhibited by DEX and MPRED, but apparently not by prednisolone (Pavek et al, 2005). In the present study, MTX resistance was also negatively correlated with ASP resistance.…”

Section: Discussionsupporting

confidence: 51%

Authenticity and drug resistance in a panel of acute lymphoblastic leukaemia cell lines

et al. 2006

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Cell lines are important models for drug resistance in acute lymphoblastic leukaemia (ALL), but are often criticised as being unrepresentative of primary disease. There are also doubts regarding the authenticity of many lines. We have characterised a panel of ALL cell lines for growth and drug resistance and compared data with that published for primary patient specimens. In contrast to the convention that cell lines are highly proliferative, those established in our laboratory grow at rates similar to estimates of leukaemic cells in vivo (doubling time 53 -442 h). Authenticity was confirmed by genetic fingerprinting, which also demonstrated the potential stability of long-term cultures. In vitro glucocorticoid resistance correlated well with that measured ex vivo, but all lines were significantly more sensitive to vincristine than primary specimens. Sensitivity to methotrexate was inversely correlated to that of glucocorticoids and L-asparaginase, indicating possible reciprocity in resistance mechanisms. A cell line identified as highly methotrexate resistant (IC 50 48000-fold higher than other lines) was derived from a patient receiving escalating doses of the drug, indicating in vivo selection of resistance as a cause of relapse. Many of these lines are suitable as models to study naturally occurring resistance phenotypes in paediatric ALL.

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Section: Discussionsupporting

confidence: 51%

Authenticity and drug resistance in a panel of acute lymphoblastic leukaemia cell lines

et al. 2006

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“…Cell Culture and Transduction Wild-type (WT) Madin-Darby canine kidney (MDCKII) cells and MDCKII cells stably transduced with human ABCG2 (32) or mouse Abcg2 (33) were described before and were kindly provided by Dr. A. Schinkel. Additionally, human embryonic kidney (HEK293) cells were stably transduced with the retroviral LZRS-IRES-GFP expression vector (34) containing the cDNA for either human ABCG2 or mouse Abcg2 as described previously (32).…”

Section: Methodsmentioning

confidence: 99%

“…Additionally, human embryonic kidney (HEK293) cells were stably transduced with the retroviral LZRS-IRES-GFP expression vector (34) containing the cDNA for either human ABCG2 or mouse Abcg2 as described previously (32). After expansion, clones were screened for expression of (functional) ABCG2/Abcg2 by determination of increased resistance to mitoxantrone in a cytotoxicity assay and by immunoblot analysis.…”

Section: Methodsmentioning

confidence: 99%

Contribution of the drug transporter ABCG2 (breast cancer resistance protein) to resistance against anticancer nucleosides

Wolf

Jansen

Yamaguchi

et al. 2008

Molecular Cancer Therapeutics

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We have studied the potential contribution of ABCG2 (breast cancer resistance protein) to resistance to nucleoside analogues. In cells transfected with DNA constructs resulting in overexpression of human or mouse ABCG2, we found resistance against cladribine, clofarabine, fludarabine, 6-mercaptopurine, and 6-mercaptopurine riboside in both MDCKII and HEK293 cells and against gemcitabine only in HEK293 cells. With Transwell studies in MDCK cells and transport experiments with vesicles from Sf9 and HEK293 cells, we show that ABCG2 is able to transport not only the nucleotide CdAMP, like several other ATP-binding cassette transporters of the ABCC (multidrug resistance protein) family, but also the nucleoside cladribine itself. Expression of ABCG2 in cells results in a substantial decrease of intracellular CdATP, explaining the resistance against cladribine. The high transport rate of cladribine and clofarabine by ABCG2 deduced from Transwell experiments raises the possibility that this transporter could affect the disposition of nucleoside analogues in patients or cause resistance in tumors. [Mol Cancer Ther 2008;7(9):3092 -102]

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“…In vitro accumulation assays were carried out as described previously (Pavek et al, 2005). Mitoxantrone (MXR, 10 µM) was used as fluorescence substrate of ABCG2, and enterolactone (100 and 200 µM) was used to inhibit the transporter (Miguel et al, 2014).…”

Section: Accumulation Assaysmentioning

confidence: 99%

Effect of bovine ABCG2 polymorphism Y581S SNP on secretion into milk of enterolactone, riboflavin and uric acid

Otero

Miguel

González-Lobato

et al. 2016

animal

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The ATP-binding cassette transporter G2/breast cancer resistance protein (ABCG2/BCRP) is an efflux protein involved in the bioavailability and milk secretion of endogenous and exogenous compounds, actively affecting milk composition. A limited number of physiological substrates have been identified. However, no studies have reported the specific effect of this polymorphism on the secretion into milk of compounds implicated in milk quality such as vitamins or endogenous compounds. The bovine ABCG2 Y581S polymorphism is described as a gain-of-function polymorphism that increases milk secretion and decreases plasma levels of its substrates. This work aims to study the impact of Y581S polymorphism on plasma disposition and milk secretion of compounds such as riboflavin (vitamin B 2 ), enterolactone, a microbiota-derived metabolite from the dietary lignan secoisolariciresinol and uric acid. In vitro transport of these compounds was assessed in MDCK-II cells overexpressing the bovine ABCG2 (WT-bABCG2) and its Y581S variant (Y581S-bABCG2). Plasma and milk levels were obtained from Y/Y homozygous and Y/S heterozygous cows. The results show that riboflavin was more efficiently transported in vitro by the Y581S variant, although no differences were noted in vivo. Both uric acid and enterolactone were substrates in vitro of the bovine ABCG2 variants and were actively secreted into milk with a two-fold increase in the milk/plasma ratio for Y/S with respect to Y/Y cows. The in vitro ABCG2-mediated transport of the drug mitoxantrone, as a model substrate, was inhibited by enterolactone in both variants, suggesting the possible in vivo use of this enterolignan to reduce ABCG2-mediated milk drug transfer in cows. The Y581S variant was inhibited to a lesser extent probably due to its higher transport capacity. All these findings point to a significant role of the ABCG2 Y581S polymorphism in the milk disposition of enterolactone and the endogenous molecules riboflavin and uric acid, which could affect both milk quality and functionality.

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Human Breast Cancer Resistance Protein: Interactions with Steroid Drugs, Hormones, the Dietary Carcinogen 2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, and Transport of Cimetidine

Cited by 256 publications

References 26 publications

Authenticity and drug resistance in a panel of acute lymphoblastic leukaemia cell lines

Authenticity and drug resistance in a panel of acute lymphoblastic leukaemia cell lines

Contribution of the drug transporter ABCG2 (breast cancer resistance protein) to resistance against anticancer nucleosides

Effect of bovine ABCG2 polymorphism Y581S SNP on secretion into milk of enterolactone, riboflavin and uric acid

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