PloS one, 2011-07, Vol.6 (7), p.e22628-e22628
2011
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- Autor(en) / Beteiligte
- Titel
- IRF4 is a suppressor of c-Myc induced B cell leukemia
- Ist Teil von
- PloS one, 2011-07, Vol.6 (7), p.e22628-e22628
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Interferon regulatory factor 4 (IRF4) is a critical transcriptional regulator in B cell development and function. We have previously shown that IRF4, together with IRF8, orchestrates pre-B cell development by limiting pre-B cell expansion and by promoting pre-B cell differentiation. Here, we report that IRF4 suppresses c-Myc induced leukemia in EμMyc mice. Our results show that c-Myc induced leukemia was greatly accelerated in the IRF4 heterozygous mice (IRF4(+/-)Myc); the average age of mortality in the IRF4(+/-)Myc mice was only 7 to 8 weeks but was 20 weeks in the control mice. Our results show that IRF4(+/-)Myc leukemic cells were derived from large pre-B cells and were hyperproliferative and resistant to apoptosis. Further analysis revealed that the majority of IRF4(+/-)Myc leukemic cells inactivated the wild-type IRF4 allele and contained defects in Arf-p53 tumor suppressor pathway. p27(kip) is part of the molecular circuitry that controls pre-B cell expansion. Our results show that expression of p27(kip) was lost in the IRF4(+/-)Myc leukemic cells and reconstitution of IRF4 expression in those cells induced p27(kip) and inhibited their expansion. Thus, IRF4 functions as a classical tumor suppressor to inhibit c-Myc induced B cell leukemia in EμMyc mice.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0022628Titel-ID: cdi_plos_journals_1305757082
- Format
- –
- Schlagworte
- Age, Analysis, Animals, Antigens, Apoptosis, B cells, Biological response modifiers, Biology, c-Myc protein, Cell cycle, Cell differentiation, Cell Proliferation, Circuits, Cyclin-Dependent Kinase Inhibitor p27 - metabolism, Expansion, Gene expression, Health aspects, Immunoglobulin M - metabolism, Immunoglobulins, Interferon, Interferon regulatory factor, Interferon regulatory factor 4, Interferon Regulatory Factors - metabolism, Kinases, Leukemia, Leukemia, B-Cell - blood, Leukemia, B-Cell - metabolism, Leukemia, B-Cell - pathology, Leukocyte Common Antigens - metabolism, Lymphocyte Count, Lymphocytes B, Lymphoma, Medicine, Mice, Mortality, Myc protein, Neoplasm Transplantation, p53 Protein, Precursor Cells, B-Lymphoid - metabolism, Precursor Cells, B-Lymphoid - pathology, Proteins, Proto-Oncogene Proteins c-myc - metabolism, Rodents, Signal Transduction, Transcription, Transgenic animals, Tumor proteins, Tumor suppressor genes, Tumor Suppressor Protein p14ARF - metabolism, Tumor Suppressor Protein p53 - metabolism, Tumor Suppressor Proteins - metabolism