Drug-transporter proteins in clinical multidrug resistance

R. J. Scheper, H. J. Broxterman, G. L. Scheffer, C. J L M Meijer, H. M. Pinedo

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)25-32
Number of pages8
JournalClinica Chimica Acta
Volume206
Issue number1-2
DOIs
StatePublished - Mar 13 1992
Externally publishedYes

Keywords

  • Exocytosis
  • Multidrug-resistance
  • P-glycoprotein
  • Transporter proteins

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry

Fingerprint Dive into the research topics of 'Drug-transporter proteins in clinical multidrug resistance'. Together they form a unique fingerprint.

Cite this