Zinc finger protein GFI-1 cooperates with myc and pim-1 in T-cell lymphomagenesis by reducing the requirements for IL-2

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.