This laboratory has been investigation genetic and biochemical changes associated with drug resistance in human tumors. We have characterized an adriamycin resistant human breast cancer cell line which has developed the phenotype of multidrug resistance. Resistance is associated with decreased drug accumulation (2-3 fold) increased activities of glutathione peroxidase (12 fold), glutathione transferase (45 fold), decreased expression of aryl hydrocarbon hydroxylase (cytochrome P1-450). We have isolated cDNA clones from this resistant cell line which encode the gP 170 membrane glycoprotein, a gene which is often, if not always, associated with the development of multidrug resistance. We have also cloned the cDNA for the anionic glutathione transferase which is transcriptionally activated in the AdrR MCF-7 cells. We have begun a study investigating the expression of the P-glycoprotein gene as well as the expression of several drug metabolizing enzymes including the anionic glutathione transferase GST-pi in the development of clinical drug resistance.
