Functional expression of murine multidrug resistance in Xenopus laevis oocytes.
The development of multidrug resistance (MDR) is associated with the overproduction of a plasma membrane glycoprotein, P glycoprotein. Here we report the functional expression of a member of the murine mdr family of proteins and show that Xenopus oocytes injected with RNA encoding the mouse mdr1b P glycoprotein develop a MDR-like phenotype. Immunological analysis indicated that oocytes injected with the mdr1b RNA synthesized a protein with the size and immunological characteristics of the mouse mdr1b P glycoprotein. These oocytes exhibited a decreased accumulation of [3H]vinblastine and showed an increased capacity to extrude the drug compared to control oocytes not expressing the P glycoprotein. In addition, competition experiments indicated that verapamil, vincristine, daunomycin, and quinidine, but not colchicine, can overcome the rapid drug efflux conferred by the expression of the mouse P glycoprotein.
Program in Molecular Biology, Memorial Sloan-Kettering Cancer Research Center, New York, NY 10021.
G
G
Castillo
J C
JC
Vera
C P
CP
Yang
S B
SB
Horwitz
O M
OM
Rosen
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D002352:Carrier Proteins / Q000378:metabolism*; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism*; D010957:Plasmids; D012313:RNA / Q000235:genetics; D014158:Transcription, Genetic; D014747:Vinblastine / Q000378:metabolism*; D014982:Xenopus laevis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000906:Antibodies; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D014747:Vinblastine; D012313:RNA