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 language | English (US) |
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Pages (from-to) | 607-649 |
Number of pages | 43 |
Journal | Annual review of genetics |
Volume | 29 |
DOIs | |
State | Published - 1995 |
Keywords
- P-glycoprotein
- chemotherapy
- episomes
- gene therapy
- multidrug resistance
ASJC Scopus subject areas
- Genetics