OVEREXPRESSION OF C-MYC PRECEDES AMPLIFICATION OF THE GENE ENCODING DIHYDROFOLATE-REDUCTASE

An experimentally inducible model system was generated in which Chines e hamster ovary cells (CHO-9) were stably transfected with an inducibl e c-myc cDNA. The induction of c-myc in these transfectants is followe d by the enhanced binding of c-Myc/Max-containing protein complexes to 5' flanking E-box sequences of the gene encoding dihydrofolate reduct ase (DHFR). Moreover, DHFR is transiently amplified. The inappropriate overproduction of the oncoprotein, therefore, seems to plays a role i n induced DHFR amplification.