Genetic analysis of the multidrug transporter.
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.
Gottesman
M M
MM
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Hrycyna
C A
CA
Schoenlein
P V
PV
Germann
U A
UA
Pastan
I
I
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000818:Animals; D030801:Animals, Genetically Modified; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005784:Gene Amplification; D005786:Gene Expression Regulation; D005819:Genetic Markers; D015316:Genetic Therapy; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000737:chemistry / Q000235:genetics / Q000628:therapy; D014176:Protein Biosynthesis; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005819:Genetic Markers