C-MYC OVEREXPRESSION ASSOCIATED DHFR GENE AMPLIFICATION IN HAMSTER, RAT, MOUSE AND HUMAN CELL-LINES

We have analysed relative DHFR gene copy numbers in nine cell fines of various cell type and species origins. The cells studied expressed ei ther low, low and inducible or constitutively elevated levels of c-Myc protein. DHFR gene amplification was observed only when c-Myc protein levels were upregulated. The amplification of the DHFR gene was trans ient in inducible cell Lines. Cell lines exhibiting constitutively der egulated c-Myc protein levels, however, showed both DHFR gene amplific ation and ongoing rearrangements of the DHFR locus. In contrast, the r elative gene copy numbers of ribonucleotide reductase R1 subunit, orni thine decarboxylase, syndecan 2, glyceraldehyde-3-phosphate-dehydrogen ase and cyclin C remained unaffected irrespective of c-Myc protein lev els, suggesting a locus-specific genomic instability of the DHFR gene in cells with deregulated c-Myc protein levels. Overall, the results o f the present study support the notion that DHFR gene amplification as a consequence of c-Myc deregulation may occur in a variety of cell li nes irrespective of their cell type and species origins.