GENETIC-ANALYSIS OF THE MULTIDRUG TRANSPORTER

The analysis of how human cancers evade chemotherapy has revealed a ri ch variety of cell-based genetic changes resulting in drug resistance. One of the best studied of these genetic alterations is increased exp ression of an ATP-dependent plasma membrane transport system known as P-glycoprotein, or the multidrug transporter. This transporter activel y effluxes a large number of natural product, hydrophobic, cytotoxic d rugs, including many important anticancer agents. This review focuses on the genetic and molecular genetic analysis of the human multidrug t ransporter, including structure-function analysis, pre- and posttransl ational regulation of expression, the role of gene amplification in in creased 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.