A tumor-suppressor function for NFATc3 in T-cell lymphomagenesis by murine leukemia virus

Blood. 2005 Nov 15;106(10):3546-52. doi: 10.1182/blood-2005-02-0493. Epub 2005 Jul 28.

Abstract

Nuclear factor of activated T cell (NFAT) transcription factors play a central role in differentiation, activation, and elimination of lymphocytes. We here report on the finding of provirus integration into the Nfatc3 locus in T-cell lymphomas induced by the murine lymphomagenic retrovirus SL3-3 and show that NFATc3 expression is repressed in these lymphomas. The provirus insertions are positioned close to the Nfatc3 promoter or a putative polyadenylated RNA (polyA) region. Furthermore, we demonstrate that NFATc3-deficient mice infected with SL3-3 develop T-cell lymphomas faster and with higher frequencies than wild-type mice or NFATc2-deficient mice. These results identify NFATc3 as a tumor suppressor for the development of murine T-cell lymphomas induced by the retrovirus SL3-3.

Publication types

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

MeSH terms

  • Animals
  • Leukemia Virus, Murine / genetics
  • Leukemia Virus, Murine / immunology*
  • Leukemia, Experimental / genetics
  • Leukemia, Experimental / immunology*
  • Leukemia, Experimental / pathology
  • Lymphoma, T-Cell / genetics
  • Lymphoma, T-Cell / immunology
  • Lymphoma, T-Cell / pathology
  • Mice
  • Mice, Inbred BALB C
  • NFATC Transcription Factors / deficiency
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / immunology*
  • Retroviridae Infections / genetics
  • Retroviridae Infections / immunology*
  • Retroviridae Infections / pathology
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / immunology*
  • Tumor Virus Infections / genetics
  • Tumor Virus Infections / immunology*
  • Tumor Virus Infections / pathology
  • Virus Integration / immunology

Substances

  • NFATC Transcription Factors
  • Nfatc3 protein, mouse
  • Tumor Suppressor Proteins