Genetic Analysis of the Multidrug Transporter

Annu Rev Genet. 1995;29:607-49. doi: 10.1146/annurev.ge.29.120195.003135.

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.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Animals
  • Animals, Genetically Modified
  • Drug Resistance, Multiple / genetics*
  • Gene Amplification
  • Gene Expression Regulation
  • Genetic Markers
  • Genetic Therapy
  • Humans
  • Mutation
  • Neoplasms / chemistry
  • Neoplasms / genetics
  • Neoplasms / therapy
  • Protein Biosynthesis
  • Protein Conformation
  • Protein Processing, Post-Translational

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Genetic Markers