c-MYC overexpression in Ba/F3 cells simultaneously elicits genomic instability and apoptosis

被引:33
作者
Fest, T
Mougey, V
Dalstein, V
Hagerty, M
Milette, D
Silva, S
Mai, S
机构
[1] CancerCare Manitoba Univ Manitoba, Manitoba Inst Cell Biol, Genom Ctr Canc Res & Diag, Winnipeg, MB R3E 0V9, Canada
[2] Inst Etud & Transfert Genes, F-25030 Besancon, France
[3] Karolinska Inst, Microbiol & Tumorbiol Ctr, Stockholm, Sweden
关键词
c-Myc; dihydrofolate reductase; genomic instability; polyploidy; apoptosis;
D O I
10.1038/sj/onc/1205274
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Overexpression of c-Myc in tumors is usually associated with cell proliferation and increased susceptibility to apoptosis. Concomitantly, c-Myc contributes to tumorigenesis by its ability to destabilize the cellular genome. Here, we examined whether c-Myc induces genomic instability and apoptosis in c-Myc-activated cells. Wildtype Myc (wt-Myc) and two mutated Myc myc box II proteins (mt-Myc) were overexpressed in IL3-dependent murine Ba/F3 cells. As expected, wt-Myc triggered apoptosis in absence of IL3. Standard karyotyping, spectral karyotyping, and fluorescent in situ hybridization (FISH) were performed before and after c-Myc activation. Structural and numerical genomic instability was detected 48 h after wt-Myc activation and included gene amplification, the formation of extrachromosomal elements (EEs), chromosome breakage, deletions, increased aneuploidy, and polyploidization. Interestingly, some cells simultaneously displayed genomic instability and apoptosis. Both wt- and mt-Myc proteins were equally potent promoters of genomic instability. However, only wt-Myc simultaneously induced genomic instability and apoptosis. Mt-Myc proteins failed to induce apoptosis, thereby generating a strong imbalance towards the survival of genomically unstable cells.
引用
收藏
页码:2981 / 2990
页数:10
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