This laboratory had been investigating 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 (23 fold), increased activities of glutathione peroxidase (12 fold), glutathione transferase (45 fold), decreased expression of aryl hydrocarbon hydroxylase (cytochrome P 1 -450). We have isolated cDNA clones from this resistant cell line which encode the gP 170 membrane glycoprotein, a gene which is often associated with the development of drug resistance. We have also cloned the cDNA for the anionic glutathione transferase GST-pi which is transcriptionally activated in the AdR MCF-7 cells. We have used gene transfection to analyze the roles of mdr-1, protein kinase C, and glutadiione S transferase pi, alpha, mur in development of drug and carcinogen resistance. We have also studied the mechanisms of regulation of mdr1, GST pi, and GSH peroxidase gene expression in human tumor cells.
