ABCMdb

PMID: 15684613

Robey RW, Steadman K, Polgar O, Bates SE
ABCG2-mediated transport of photosensitizers: potential impact on photodynamic therapy.
Cancer Biol Ther. 2005 Feb;4(2):187-94. Epub 2005 Feb 8., [PubMed]

Sentences

No. Mutations Sentence Comment

90 ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly Mutations in the ABCG2 gene which cause amino acid changes at position 482 are known to alter the substrate specificity of the protein.26,27,34 Thus, accumulation studies with the photosensitizers were repeated in HEK-293 cells stably transfected with wild-type (R482) or mutant (R482G, R482T) ABCG2. Login to comment 94 ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly ABCG2-transfected HEK-293 cells expressing comparable levels of wild-type (482R) or mutant (R482G, R482T) ABCG2 were incubated in the desired photosensitizer (50 µM Ce6, 10 µM MPPa, 25 µM m-THPP, 25 µM m-THPC or 25 µM HpIX) for 30 min with or without 10 µM FTC, washed, and then incubated for 60 min continuing with (dashed line) or without (solid line) FTC. Login to comment 148 ABCG2 p.Gln141Lys ABCG2 p.Gln141Lys ABCG2 p.Gln141Lys ABCG2 p.Gln141Lys ABCG2 p.Gln141Lys ABCG2 p.Gln141Lys We and others described a 421C>A nonsynonymous single nucleotide polymorphism (glutamine to lysine, Q141K, amino acid change) that impairs the transport activity of the protein.40-42 Cells expressing Q141K ABCG2 were shown to be more sensitive to the ABCG2 substrate drugs mitoxantrone, SN-38, topotecan and diflomotecan compared to cells expressing comparable cell surface levels of wild-type protein.42 Expression of the Q141K SNP has also been linked to higher serum levels of diflomotecan in patients receiving the drug orally, suggesting the Q141K polymorphism may affect the pharmacokinetics of ABCG2 substrate drugs.43 In light of the affect of the Q141K polymoprhism on the disposition of ABCG2 substrate drugs, it is tempting to speculate that the Q141K polymorphism may play a role in this observed extended sensitivity due to decreased transporter activity of the resulting ABCG2 protein. Login to comment 154 ABCG2 p.Gln141Lys These results suggest that PDT with photosensitizers that are ABCG2 substrates may be rendered less effective in ABCG2 expressing cancers and that the Q141K polymorphism in ABCG2 may explain increases in the duration of photosensitivity in some patients. Login to comment