title: c-MYC overexpression in Ba/F3 cells simultaneously elicits genomic instability and apoptosis.
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.
authors.affiliation: Hematology Department, University Hospital Jean Minjoz, 20539 Besançon Cedex, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Fest
authors.forename: Virginie
authors.initials: V
authors.lastname: Mougey
authors.forename: Véronique
authors.initials: V
authors.lastname: Dalstein
authors.forename: Marlon
authors.initials: M
authors.lastname: Hagerty
authors.forename: Danielle
authors.initials: D
authors.lastname: Milette
authors.forename: Santiago
authors.initials: S
authors.lastname: Silva
authors.forename: Sabine
authors.initials: S
authors.lastname: Mai
mesh_terms: D000782:Aneuploidy; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002051:Burkitt Lymphoma / Q000235:genetics; D002460:Cell Line / Q000166:cytology / Q000187:drug effects; D019457:Chromosome Breakage; D020223:Chromosome Painting; D002875:Chromosomes / Q000235:genetics* / Q000648:ultrastructure; D016259:Genes, myc; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D007621:Karyotyping; D051379:Mice; D009154:Mutation; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection
chemical_list: D007377:Interleukin-3; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins