ABCMdb

PMID: 17032904

Breedveld P, Pluim D, Cipriani G, Dahlhaus F, van Eijndhoven MA, de Wolf CJ, Kuil A, Beijnen JH, Scheffer GL, Jansen G, Borst P, Schellens JH
The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models.
Mol Pharmacol. 2007 Jan;71(1):240-9. Epub 2006 Oct 10., [PubMed]

Sentences

No. Mutations Sentence Comment

249 ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly For instance, Honjo et al. (2001) showed that cells with R482T and R482G BCRP displayed altered levels of resistance to anthracyclines, SN-38, and topotecan. Login to comment 250 ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly For (anti)folates, vesicular studies have shown that folic acid, MTX, and MTX-glu2 are transported by wild-type BCRP (ABCG2-R482), used in our studies, but not by mutant BCRP (ABCG2-R482T and ABCG2-R482G) (Chen et al., 2003; Mitomo et al., 2003; Volk and Schneider, 2003), suggesting that changes in the protein structure indeed have consequences for the (anti)folate substrate specificity of BCRP. Login to comment 252 ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly However, recent observations by Shafran et al. (2005) demonstrated that intact cells harboring the R482G and R482T amino acid replacements were markedly resistant to short-term exposures to antifolates, including MTX, in association with a poor accumulation of MTX-diglutamates. Login to comment