@article{6a3b221c2f624c50ba2c5dafc0d0ee87,
title = "Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2",
abstract = "Transfection of multidrug resistance proteins (MRPs) MRP1 and MRP2 in human ovarian carcinoma 2008 cells conferred a marked level of resistance to short-term (1-4 h) exposure to the polyglutamatable antifolates methotrexate (MTX; 21-74-fold), ZD1694 (4-138-fold), and GW1843 (101-156-fold). Evidence for MRP-mediated antifolate efflux relies upon the following findings: (a) a 2-3.3-fold lower accumulation of [3H]MTX and subsequent reduced formation of long-chain polyglutamate forms of MTX; (b) reversal of MTX resistance by probenecid in both transfectants, and (c) ATP-dependent uptake of [3H]MTX in inside-out vesicles of MRP1 and MRP2 transfectants. This report provides a mechanistic basis for resistance to polyglutamatable antifolates through an MRP-mediated drug extrusion.",
keywords = "ATP Binding Cassette Transporter, Subfamily B/antagonists & inhibitors, ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors, ATP-Binding Cassette Transporters/antagonists & inhibitors, Adenosine Triphosphate/metabolism, Antimetabolites, Antineoplastic/metabolism, Drug Resistance, Multiple/genetics, Drug Resistance, Neoplasm/genetics, Female, Folic Acid Antagonists/metabolism, Glutamates/metabolism, Humans, Indoles/metabolism, Isoindoles, Methotrexate/metabolism, Ovarian Neoplasms/genetics, Quinazolines/metabolism, Thiophenes/metabolism, Transfection, Tumor Cells, Cultured/drug effects",
author = "Hooijberg, {J H} and Broxterman, {H J} and M Kool and Assaraf, {Y G} and Peters, {G J} and P Noordhuis and Scheper, {R J} and P Borst and Pinedo, {H M} and G Jansen",
year = "1999",
month = "6",
day = "1",
language = "English",
volume = "59",
pages = "2532--5",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "11",
}