Genetic analysis of the multidrug transporter

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

Research output: Contribution to journalReview article

437 Citations (Scopus)

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
StatePublished - Jan 1 1995

Fingerprint

MDR Genes
Gene Amplification
P-Glycoprotein
Biological Products
Drug Resistance
Knockout Mice
Genetic Therapy
Antineoplastic Agents
Molecular Biology
Adenosine Triphosphate
Cell Membrane
Drug Therapy
Pharmaceutical Preparations
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Genetics

Cite this

Genetic analysis of the multidrug transporter. / Gottesman, M. M.; Hrycyna, C. A.; Schoenlein, Patricia V; Germann, U. A.; Pastan, I.

In: Annual review of genetics, Vol. 29, 01.01.1995, p. 607-649.

Research output: Contribution to journalReview article

Gottesman, M. M. ; Hrycyna, C. A. ; Schoenlein, Patricia V ; Germann, U. A. ; Pastan, I. / Genetic analysis of the multidrug transporter. In: Annual review of genetics. 1995 ; Vol. 29. pp. 607-649.
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