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

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...

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Bibliographic Details
Published in:Blood 2005-11, Vol.106 (10), p.3546-3552
Main Authors: Glud, Sys Zoffmann, Sørensen, Annette Balle, Andrulis, Mindaugas, Wang, Bruce, Kondo, Eisaku, Jessen, Randi, Krenacs, Laszlo, Stelkovics, Eva, Wabl, Matthias, Serfling, Edgar, Palmetshofer, Alois, Pedersen, Finn Skou
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Hematologic and hematopoietic diseases
Leukemia Virus, Murine - genetics
Leukemia Virus, Murine - immunology
Leukemia, Experimental - genetics
Leukemia, Experimental - immunology
Leukemia, Experimental - pathology
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Lymphoma, T-Cell - genetics
Lymphoma, T-Cell - immunology
Lymphoma, T-Cell - pathology
Medical sciences
Mice
Mice, Inbred BALB C
Neoplasia
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
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Summary: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2005-02-0493