Zinc Finger Protein GFI-1 Cooperates With Myc and pim-1 in T-cell Lymphomagenesis by Reducing the Requirements for IL-2

Oncogene. 1996 Apr 18;12(8):1789-801.

Abstract

The clonality of lymphomas that originate in myc/pim-1 bitransgenic mice due to synergistic action of both oncogenes indicates the requirement of additional events for progression to full malignancy. To isolate genes that cooperate with both myc and pim-1, we have used provirus tagging with E mu L-myc/pim-1 double transgenic mice. We find accelerated tumour formation in infected animals and show that the gfi-1 gene and neighbouring loci on mouse chromosome 5 are occupied by proviruses in about 53% of the tumours leading in all cases to high level gfi-1 expression. In agreement with data from Gilks et al. (1993) we find that forced expression of the gfi-1 encoded zinc finger protein in IL-2 dependent T-cells provokes increased survival upon IL-2 depletion and we present evidence that this occurs at least in part through stimulation of proliferation. Our data suggest that gfi-1 is a proto-oncogene cooperation with both myc and pim-1 genes in T-cell lymphomagenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Caenorhabditis elegans Proteins*
  • Cell Cycle / genetics
  • Chromosome Mapping
  • Conserved Sequence
  • DNA Transposable Elements
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation, Neoplastic
  • Genes, myc*
  • Helminth Proteins / genetics
  • Homeodomain Proteins*
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism*
  • Lymphoma, T-Cell / genetics*
  • Lymphoma, T-Cell / pathology
  • Lymphoma, T-Cell / virology
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Moloney murine leukemia virus / genetics
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-pim-1
  • Trans-Activators*
  • Transcription Factors*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Caenorhabditis elegans Proteins
  • DNA Transposable Elements
  • DNA-Binding Proteins
  • Gfi1 protein, mouse
  • Helminth Proteins
  • Homeodomain Proteins
  • Interleukin-2
  • Proto-Oncogene Proteins
  • Trans-Activators
  • Transcription Factors
  • pal-1 protein, C elegans
  • Pim1 protein, mouse
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-pim-1

Associated data

  • GENBANK/U78312