p53-dependent senescence delays Emu-myc-induced B-cell lymphomagenesis

Oncogene. 2010 Mar 4;29(9):1260-9. doi: 10.1038/onc.2009.423. Epub 2009 Nov 23.


The effect of p53-dependent cell-cycle arrest and senescence on Emu-myc-induced B-cell lymphoma development remains controversial. To address this question, we crossed Emu-myc mice with the p53(515C) mutant mouse, encoding the mutant p53R172P protein that retains the ability to activate the cell-cycle inhibitor and senescence activator p21. Importantly, this mutant lacks the ability to activate p53-dependent apoptotic genes. Hence, Emu-myc mice that harbor two p53(515C) alleles are completely defective for p53-dependent apoptosis. Both Emu-myc::p53(515C/515C) and Emu-myc::p53(515C/+) mice survive significantly longer than Emu-myc::p53(+/-) mice, indicating the importance of the p53-dependent non-apoptotic pathways in B-cell lymphomagenesis. In addition, the p53(515C) allele is deleted in several Emu-myc::p53(515C/+) lymphomas, further emphasizing the functionality of p53R172P in tumor inhibition. Lymphomas from both Emu-myc::p53(515C/515C) and Emu-myc::p53(515C/+) mice retain the ability to upregulate p21, resulting in cellular senescence. Senescence-associated beta-galactosidase (SA beta-gal) activity was observed in lymphomas from Emu-myc::p53(+/+), Emu-myc::p53(515C/515C) and Emu-myc::p53(515C /+) mice but not in lymphomas isolated from Emu-myc::p53(+/-) mice. Thus, in the absence of p53-dependent apoptosis, the ability of p53R172P to induce senescence leads to a significant delay in B-cell lymphoma development.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / drug effects
  • Aging / immunology
  • Aging / physiology*
  • Animals
  • Apoptosis / drug effects
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • Cyclin-Dependent Kinase Inhibitor p16 / pharmacology
  • Dromaiidae
  • Genes, p53 / genetics
  • Genes, p53 / immunology*
  • Genes, p53 / physiology
  • Lymphoma / immunology
  • Lymphoma / pathology*
  • Lymphoma / physiopathology
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / pathology*
  • Mice
  • Proto-Oncogene Proteins c-myc / pharmacology
  • Tumor Suppressor Protein p53 / pharmacology
  • beta-Galactosidase / metabolism


  • Cyclin-Dependent Kinase Inhibitor p16
  • Proto-Oncogene Proteins c-myc
  • Tumor Suppressor Protein p53
  • beta-Galactosidase