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 (DHFR) gene. This study was performed to determine whether additional chromosomal aberrations occur when c-Myc protein levels are up-regulated for prolonged periods. To this end, we have used Rat1A-MycER cells, which allow the experimental regulation of Myc protein levels. We examined the genomic stability of Rat1A-MycER cells cultivated in either the 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 breakage, the formation of circular chromosomal structures, chromosome fusions, and extrachromosomal elements.
Mai
S
S
Manitoba Institute of Cell Biology, Winnipeg, Canada. SMAI@CC.UMANITOBA.CA
Fluri
M
M
Siwarski
D
D
Huppi
K
K
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002869:Chromosome Aberrations; D017931:DNA Primers / Q000235:genetics; D005786:Gene Expression Regulation; D017404:In Situ Hybridization, Fluorescence; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D051381:Rats; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D015854:Up-Regulation
D017931:DNA Primers; D016271:Proto-Oncogene Proteins c-myc; D013762:Tetrahydrofolate Dehydrogenase