Sensitivity to Myc-Induced Apoptosis Is Retained in Spontaneous and Transplanted Lymphomas of CD2-mycER Mice

Oncogene. 2000 Feb 10;19(6):773-82. doi: 10.1038/sj.onc.1203321.

Abstract

To study the effects of the Myc oncoprotein in a regulatable in vivo system, we generated lines of transgenic mice in which a tamoxifen inducible Myc fusion protein (c-mycER) is expressed under the control of the CD2 locus control region. Activation of the Myc oncoprotein resulted in both proliferation and apoptosis in vivo. Lines with a high transgene copy number developed spontaneous lymphomas at low frequency, but the tumour incidence was significantly increased with tamoxifen treatment. Surprisingly, we found that cellular sensitivity to Myc-induced apoptosis was retained in tumours from these mice and in most lymphoma cell lines, even when null for p53. Resistance to Myc-induced apoptosis could be conferred on these cells by co-expression of Bcl-2. However, acquired resistance is clearly not an obligatory progression event as sensitivity to apoptosis was retained in transplanted tumours in athymic mice. In conclusion, lymphomas arising in CD2-mycER mice retain the capacity to undergo apoptosis in response to Myc activation and show no phenotypic evidence of the presence of an active dominant inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • CD2 Antigens / genetics
  • Cell Cycle / drug effects
  • Cell Division / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genes, Synthetic
  • Genes, bcl-2
  • Genes, myc*
  • Humans
  • In Situ Nick-End Labeling
  • Lymphoma / genetics
  • Lymphoma / pathology*
  • Mice
  • Mice, Nude
  • Mice, Transgenic
  • Neoplasm Transplantation
  • Proto-Oncogene Proteins c-myc / physiology*
  • Receptors, Estrogen / drug effects
  • Receptors, Estrogen / genetics
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • Tamoxifen / analogs & derivatives
  • Tamoxifen / pharmacology
  • Thymus Neoplasms / genetics
  • Thymus Neoplasms / pathology*

Substances

  • CD2 Antigens
  • Proto-Oncogene Proteins c-myc
  • Receptors, Estrogen
  • Recombinant Fusion Proteins
  • Tamoxifen
  • afimoxifene