Abstract
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. Wild-type 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.
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Acknowledgements
We thank Dr T Littlewood (ICRF, London) for providing the pBpuro Myc-ERTM vector, Pr J-Y Cahn for its support. We thank Dr TI Kuschak for critical reading of this manuscript. Research conducted in France was supported by the Faculty of Medicine Besançon Research Development Fund, by grants from Fondation de France, Paris, and Léderlé SA, and Amgen SA pharmaceutical companies. V Mougey is supported by the Ministère de l'Emploi, Programme Emploi-Jeune and the Etablissement Français du Sang de Bourgogne-Franche Comté. Research conducted in Canada was supported by the Canadian Foundation of Innovation, CancerCare Manitoba, and NSERC.
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Fest, T., Mougey, V., Dalstein, V. et al. c-MYC overexpression in Ba/F3 cells simultaneously elicits genomic instability and apoptosis. Oncogene 21, 2981–2990 (2002). https://doi.org/10.1038/sj.onc.1205274
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DOI: https://doi.org/10.1038/sj.onc.1205274
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