PMID: 16404634

Gupta A, Dai Y, Vethanayagam RR, Hebert MF, Thummel KE, Unadkat JD, Ross DD, Mao Q
Cyclosporin A, tacrolimus and sirolimus are potent inhibitors of the human breast cancer resistance protein (ABCG2) and reverse resistance to mitoxantrone and topotecan.
Cancer Chemother Pharmacol. 2006 Sep;58(3):374-83. Epub 2006 Jan 11., [PubMed]
Sentences
No. Mutations Sentence Comment
163 ABCG2 p.Arg482Gly
X
ABCG2 p.Arg482Gly 16404634:163:72
status: VERIFIED
view ABCG2 p.Arg482Gly details
 CsA has been shown to inhibit ATPase activity of wild-type BCRP and its R482G mutant [27, 30], therefore, it is presumed Table 1 Effect of CsA, tacrolimus and sirolimus on mitoxantrone and topotecan toxicity in HEK/482R and HEK/vector control cells DMSO CsA Tacrolimus Sirolimus 2 lM 5 lM 2 lM 5 lM 2 lM 5 lM IC50 (nM) of topotecan HEK/482R 182.1±30.2 66.7±11.2* 47.3±13.4* 45.7±14.6* 22.5±17.1** 39.8±25.1* 17.8±14.4** HEK/vector 10.9±0.4 11.9±0.9 13.2±4.4 9.1±2.7 12.9±4.0 12.0±4.0 10.4±1.7 RR 16.7 5.6 3.6 5.0 1.7 2.3 1.7 IC50 (nM) of mitoxantrone HEK/482R 2574.9±2134.6 63.6±9.7* 36.1±17.8* 64.8±35.7* 17.1±13.8* 51.4±37.3* 22.6±12.8* HEK/vector 198.8±105.7 14.9±13.2* 21.9±18.1* 24.9±30.4* 16.9±10.5* 20.5±17.9* 24.2±38.2* RR 13.0 4.3 1.7 2.6 1.0 2.5 0.9 Cytotoxicity studies were performed and IC50 values (mean ± S.D., n=3-4 independent experiments) were determined as described in ''Materials and methods``. Login to comment 168 ABCG2 p.Arg482Thr
X
ABCG2 p.Arg482Thr 16404634:168:134
status: VERIFIED
view ABCG2 p.Arg482Thr details
 Subsequently, these authors showed that the MCF-7/AdrVp subline, which does not express P-gp, expresses high levels of a BCRP mutant (R482T) which can transport daunorubicin [10]. Login to comment