ABCMdb

PMID: 19633067

Deeken JF, Robey RW, Shukla S, Steadman K, Chakraborty AR, Poonkuzhali B, Schuetz EG, Holbeck S, Ambudkar SV, Bates SE
Identification of compounds that correlate with ABCG2 transporter function in the National Cancer Institute Anticancer Drug Screen.
Mol Pharmacol. 2009 Nov;76(5):946-56. Epub 2009 Jul 24., [PubMed]

Sentences

No. Mutations Sentence Comment

23 ABCG2 p.Gln141Lys One nonsynonymous substitution, 421CϾA (dbSNP 914CϾA, rs2231142), leads to an amino acid substitution of lysine for glutamine at position 141 and has been shown to result in lower plasma membrane expression, reduced drug efflux, and reduced ATPase activity (Imai et al., 2002; Mizuarai et al., 2004; Morisaki et al., 2005). Login to comment 135 ABCG2 p.Gln141Lys DNA from 59 of the NCI-60 cell lines were genotyped to identify the presence of the Q141K allelic variant, previously shown to have diminished function compared with wild-type ABCG2 (Imai et al., 2002; Morisaki et al., 2005), as well as a SNP variant in the first intron of the gene recently found to correlate with chemotherapy toxicity in vivo (Rudin et al., 2008). Login to comment 137 ABCG2 p.Gln141Lys For the Q141K SNP, 12 cell lines were found to contain a variant allele. Login to comment 139 ABCG2 p.Gln141Lys The other 10 lines were heterozygous, containing one Q141K variant allele (A549, COLO205, HCT116, SF295, MALME-3M, SK-OV-3, CAKI-1, HOP62, HOP92, and MDA-MB-231). Login to comment 143 ABCG2 p.Gln141Lys To determine whether these variants affected the correlation between gene expression and transporter function, the scatter plot analysis comparing expression with function was repeated after excluding those cell lines with the Q141K SNP or the intron 1 SNP. Login to comment 165 ABCG2 p.Gln141Lys ABCG2 p.Gln166Glu ABCG2 p.Gln166Glu ABCG2 p.Ser248Pro ABCG2 p.Ser248Pro Nucleotide Change Amino Acid Reference Sequence Cell Lines Heterozygote Variants Homozygote Variants Intron 1 rs2622604 MOLT4, HOP-92, HCC2998, SF539, SNB19, SNB75, U251, SKMEL5, OVCAR3, OVCAR8, RXF393, TK10, NCI ADR-RES, MDA-MB-231, HS578T, 786-0 SW620, OVCAR 5, BT549, T47D 914CϾA Q141K rs2231142 A549, COLO205, HCT116, SF295, MALME-3M, SKOV-3, CAKI-1, HOP62, HOP92, MDA-MB-231 LOX IMVI, A498 862CϾT Y123Y rs2231139 None None 989CϾG Q166E rs1061017 None None 1057AϾG G188G rs3116439 None None 1116TϾC F208S rs1061018 None None 1235TϾC S248P rs3116448 None None 1493GϾT E334* rs3201997 None None levels of P-gp or MRP1 did not improve PCCs (data not shown). Login to comment