EXPRESSION OF A TUMOR-SUPPRESSOR GENE AND OF VARIOUS PROTOONCOGENES IN HUMAN AND MURINE ADRIAMYCIN-RESISTANT AND SENSITIVE CELL-LINES

Besides established mechanisms involved in cellular drug resistance in cluding P-glycoprotein overexpression, topoisomerase alterations and x enobiotic detoxification, the hypothesis that proto-oncogene activatio n might also play a role in cell resistance has been postulated. This hypothesis has been tested by comparing the expression of various prot o-oncogenes involved in signal transduction pathways (c-H-ras, c-g-ras , c-mil, c-myc, c-myb, c-fos), as well as the mdr gene and a tumor sup pressor gene (p53) in different adriamycin-resistant (acquired or de n ovo) or sensitive cell lines, The implication of these variations in t he process of chemoresistance is discussed.