Genetic analysis of the multidrug transporter

M. M. Gottesman, C. A. Hrycyna, P. V. Schoenlein, U. A. Germann, I. Pastan

Research output: Contribution to journalReview article

439 Scopus citations

Abstract

The analysis of how human cancers evade chemotherapy has revealed a rich variety of cell-based genetic changes resulting in drug resistance. One of the best studied of these genetic alterations is increased expression of an ATP-dependent plasma membrane transport system, known as P-glycoprotein, or the multidrug transporter. This transporter actively effluxes a large number of natural product, hydrophobic, cytotoxic drugs, including many important anticancer agents. This review focuses on the genetic and molecular genetic analysis of the human multidrug transporter, including structure-function analysis, pre- and posttranslational regulation of expression, the role of gene amplification in increased expression, and the properties of transgenic and 'knock-out' mice. One important feature of the MDR gene is its potential for the development of new selectable vectors for human gene therapy.

Original languageEnglish (US)
Pages (from-to)607-649
Number of pages43
JournalAnnual review of genetics
Volume29
DOIs
Publication statusPublished - Jan 1 1995

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Keywords

  • P-glycoprotein
  • chemotherapy
  • episomes
  • gene therapy
  • multidrug resistance

ASJC Scopus subject areas

  • Genetics

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