Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2

Jan Hendrik Hooijberg; Henk J. Broxterman; Marcel Kool; Yehuda G. Assaraf; Godefridus J. Peters; Paul Noordhuis; Rik J. Scheper; Piet Borst; Herbert M. Pinedo; Gerrit Jansen

Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2

Jan Hendrik Hooijberg, Henk J. Broxterman, Marcel Kool, Yehuda G. Assaraf, Godefridus J. Peters, Paul Noordhuis, Rik J. Scheper, Piet Borst, Herbert M. Pinedo, Gerrit Jansen

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

420 Citaten (Scopus)

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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.

Originele taal-2	Engels
Pagina's (van-tot)	2532-2535
Aantal pagina's	4
Tijdschrift	Cancer Research
Volume	59
Nummer van het tijdschrift	11
Status	Gepubliceerd - 1 jun. 1999
Extern gepubliceerd	Ja

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@article{2704a723814d4885a83c575f6719a18b,

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.",

author = "Hooijberg, {Jan Hendrik} and Broxterman, {Henk J.} and Marcel Kool and Assaraf, {Yehuda G.} and Peters, {Godefridus J.} and Paul Noordhuis and Scheper, {Rik J.} and Piet Borst and Pinedo, {Herbert M.} and Gerrit Jansen",

year = "1999",

month = jun,

day = "1",

language = "English",

volume = "59",

pages = "2532--2535",

journal = "Cancer Research",

issn = "0008-5472",

publisher = "American Association for Cancer Research Inc.",

number = "11",

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TY - JOUR

T1 - Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2

AU - Hooijberg, Jan Hendrik

AU - Broxterman, Henk J.

AU - Kool, Marcel

AU - Assaraf, Yehuda G.

AU - Peters, Godefridus J.

AU - Noordhuis, Paul

AU - Scheper, Rik J.

AU - Borst, Piet

AU - Pinedo, Herbert M.

AU - Jansen, Gerrit

PY - 1999/6/1

Y1 - 1999/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0033152212&partnerID=8YFLogxK

M3 - Article

C2 - 10363967

AN - SCOPUS:0033152212

SN - 0008-5472

VL - 59

SP - 2532

EP - 2535

JO - Cancer Research

JF - Cancer Research

IS - 11

ER -

Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2

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