GENOMIC INSTABILITY IN MYCER-ACTIVATED RAT1A-MYCER CELLS

The deregulated expression of c-Myc protein is associated with the non -random locus-specific amplification of the dihydrofolate reductase (D HFR) gene. This study was performed to determine whether additional ch romosomal aberrations occur when c-Myc protein levels are up-regulated for prolonged periods. To this end, we have used Rat1A-MycER cells, w hich allow the experimental regulation of Myc protein levels. We exami ned the genomic stability of Rat1A-MycER cells cultivated in either th e absence or the presence of estrogen, which reportedly activates the chimeric MycER protein in these cells. Following prolonged periods of MycER activation, Rat1A-Mycer cells exhibited irreversible chromosomal aberrations. The aberrations included numerical changes, chromosome b reakage, the formation of circular chromosomal structures, chromosome fusions, and extrachromosomal elements.