ABCMdb

ABCC1 p.Asp248Trp

Predicted by SNAP2:	A: D (66%), C: D (66%), E: N (57%), F: D (71%), G: D (75%), H: D (66%), I: D (75%), K: D (85%), L: D (71%), M: D (59%), N: D (63%), P: D (85%), Q: D (66%), R: D (80%), S: D (66%), T: D (71%), V: D (75%), W: D (85%), Y: D (71%),
Predicted by PROVEAN:	A: D, C: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D,

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[hide] Modulation of multidrug resistance-associated prot... Cancer Chemother Pharmacol. 2003 Feb;51(2):161-6. Epub 2002 Dec 3. Tsang WP, Chau SP, Fung KP, Kong SK, Kwok TT
Modulation of multidrug resistance-associated protein 1 (MRP1) by p53 mutant in Saos-2 cells.
Cancer Chemother Pharmacol. 2003 Feb;51(2):161-6. Epub 2002 Dec 3., [PMID:12647018]

Abstract [show]
The p53 tumor suppressor gene is one of the most frequently mutated genes in human cancer and the mutation is correlated with a poor prognosis in cancer therapy. Upregulation of multidrug resistance-associated protein 1 (MRP1) and increase in drug resistance have been found to be induced by p53 mutation. Human osteosarcoma Saos-2 cells, a p53-null cell line, was transfected with p53 with mutations at codon 143 (V to A), 175 (R to H), 248 (R to W), 273 (R to H) and 281 (D to G). Among the different transfectants, overexpression (about 42-fold) of MRP1 was detected in p53-R175H cells. Furthermore, the p53-R175H cells were 2.5-fold more resistant to doxorubicin (DOX) and had a 4-fold greater DOX efflux rate than the control cells 1 h after DOX treatment. Transfection with antisense MRP1 oligonucleotides demonstrated a DOX sensitization effect (about 2-fold) in p53-R175H transfectants but not in control cells. In addition, transfection with antisense p53 oligonucleotides greatly suppressed MRP1 expression and reversed DOX resistance in p53-R175H cells but had no effect in control cells. The results suggested that p53-R175H might induce MRP1 expression and DOX resistance in cells.

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27 Human osteosarcoma Saos-2 cells, a p53-null cell line, were transfected with five different p53 mutants (V143A, R175H, D248W, R273H and D281G). Login to comment