Drug-transporter proteins in clinical multidrug resistance.
Upon exposure to chemotherapeutic drugs, mammalian cells can acquire resistance to structurally and functionally unrelated compounds, a property known as multidrug resistance (MDR). One MDR mechanism, i.e. by the overexpression of a plasma membrane protein, P-glycoprotein (P-gp), has been identified at the molecular level. The mdr1 gene-encoded P-gp acts as a drug efflux pump, lowering intracellular drug concentration by active extrusion of drugs from the cell. The role of P-gp in determining clinical resistance to multiple anticancer drugs is likely to be largely different for various tumor types. Recently we selected a monoclonal antibody (mAb LRP56) for strong, granular cytoplasmic reactivity with MDR tumor cell lines without P-gp (over)expression. None or weak reactivity was observed with parental and P-gp positive cell lines. We hypothesize that as yet-undefined drug transport-mediating proteins are inserted in intracellular membranes lining the exocytotic compartment and thus may contribute to clinical multidrug resistance.
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
R J
RJ
Scheper
H J
HJ
Broxterman
G L
GL
Scheffer
C J
CJ
Meijer
H M
HM
Pinedo
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004351:Drug Resistance; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm