Overexpression of c-myc precedes amplification of the gene encoding dihydrofolate reductase.

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