THE ROLE OF THE MDR1 (P-GLYCOPROTEIN) GENE IN MULTIDRUG RESISTANCE INVITRO AND INVIVO

This review describes the studies that address the role of the MDR1 (P-glycoprotein) gene in multidrug resistance in cell lines selected in vitro and in clinical cancer. Molecular genetic studies have demonstrated that expression of P-glycoprotein, an efflux pump acting at diverse lipophilic compounds, is sufficient to provide resistance to a large number of lipophilic drugs in tissue culture. The MDR1 gene is expressed in several normal human tissues associated with secretory or barrier functions and in some bone marrow and blood cells; including hematopoietic progenitor cells. MDRl expression in clinical cancer is often found in untreated tumors of different types. Several studies showed a correlation between MDRl expression and tumor resistance to combination chemotherapy. MDRl expression in untreated tumors may reflect their origin from MDRl-positive normal cells or cellular changes associated with neoplastic transformation or progression. MDRl expression in some types of cancer may be a marker of a more aggressive subpopulation of tumor cells, possessing multiple mechanisms for resistance to treatment.