E mu N- and E mu L-myc cooperate with E mu pim-1 to generate lymphoid tumors at high frequency in double-transgenic mice

Oncogene. 1991 Nov;6(11):1941-8.

Abstract

Transgenic mice that contain the L-myc gene under the control of the immunoglobulin heavy-chain enhancer (E mu) express the transgene preferentially in T cells, develop thymic hyperplasia and are predisposed to T-cell lymphomas. An analogous E mu N-myc transgene is expressed preferentially in pre-B and B cells and provokes the development of B-cell neoplasias. Animals with an E mu pim-1 construct express the transgene in both B and T cells, but succumb to T-cell lymphomas. Complementation of the E mu N- and L-myc transgenic mice by breeding with E mu pim-1 animals leads to much more rapid development and a dramatically higher incidence of lymphoid malignancies, but the lineage specificity prescribed by the E mu N- and L-myc transgenes is maintained. The different oncogenic potential of myc genes is illustrated by the average latency period of tumor manifestation in double transgenics. Whereas c-myc/pim-1 animals develop pre-B-cell leukemia prenatally, the mean latency period for N-myc/pim-1 and L-myc/pim-1 mice is 36 and 94 days respectively. The N- and L-myc transgenes are expressed at high levels in tumors from double transgenic mice, but expression of the endogenous c- and N-myc genes is undetectable, directly implicating the myc transgenes in the tumor formation process.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Northern
  • Blotting, Southern
  • Down-Regulation
  • Enhancer Elements, Genetic / physiology*
  • Gene Expression Regulation, Neoplastic / physiology*
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain
  • Gene Rearrangement, B-Lymphocyte, Light Chain
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Genes, myc / physiology*
  • Immunoglobulin kappa-Chains / genetics
  • Lymphocyte Activation
  • Lymphoma / genetics*
  • Mice
  • Mice, Transgenic
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins c-myc / biosynthesis
  • Proto-Oncogene Proteins c-pim-1
  • Transcription, Genetic

Substances

  • Immunoglobulin kappa-Chains
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myc
  • Pim1 protein, mouse
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-pim-1