Zinc finger protein GFI-1 cooperates with myc and pim-1 in T-cell lymphomagenesis by reducing the requirements for IL-2.
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.
Zörnig
M
M
Insitut für Molekularbiologie und Tumorforschung (IMT), Philipps Universität Marburg, Germany.
Schmidt
T
T
Karsunky
H
H
Grzeschiczek
A
A
Möröy
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D029742:Caenorhabditis elegans Proteins; D002453:Cell Cycle / Q000235:genetics; D002874:Chromosome Mapping; D017124:Conserved Sequence; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D015801:Helminth Proteins / Q000235:genetics; D018398:Homeodomain Proteins; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000473:pathology / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D051573:Proto-Oncogene Proteins c-pim-1; D015534:Trans-Activators; D014157:Transcription Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D029742:Caenorhabditis elegans Proteins; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; C079873:Gfi1 protein, mouse; D015801:Helminth Proteins; D018398:Homeodomain Proteins; D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C068665:pal-1 protein, C elegans; C496636:Pim1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1