Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Deutsch, AJ; Rinner, B; Wenzl, K; Pichler, M; Troppan, K; Steinbauer, E; Schwarzenbacher, D; Reitter, S; Feichtinger, J; Tierling, S; Prokesch, A; Scheideler, M; Krogsdam, A; Thallinger, GG; Schaider, H; Beham-Schmid, C; Neumeister, P.
NR4A1-mediated apoptosis suppresses lymphomagenesis and is associated with a favorable cancer-specific survival in patients with aggressive B-cell lymphomas.
Blood. 2014; 123(15):2367-2377
Doi: 10.1182/blood-2013-08-518878
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- Führende Autor*innen der Med Uni Graz
- Deutsch Alexander
- Neumeister Peter
- Co-Autor*innen der Med Uni Graz
- Beham-Schmid Christine
- Feichtinger Julia
- Ninaus Daniela
- Pichler Martin
- Prochazka Katharina
- Prokesch Andreas
- Reitter Sonja
- Rinner Beate
- Schaider Helmut
- Steinbauer Elisabeth
- Wenzl Kerstin
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- Abstract:
- NR4A1 (Nur77) and NR4A3 (Nor-1) function as tumor suppressor genes as demonstrated by the rapid development of acute myeloid leukemia in the NR4A1 and NR4A3 knockout mouse. The aim of our study was to investigate NR4A1 and NR4A3 expression and function in lymphoid malignancies. We found a vastly reduced expression of NR4A1 and NR4A3 in chronic lymphocytic B-cell leukemia (71%), in follicular lymphoma (FL, 70%), and in diffuse large B-cell lymphoma (DLBCL, 74%). In aggressive lymphomas (DLBCL and FL grade 3), low NR4A1 expression was significantly associated with a non-germinal center B-cell subtype and with poor overall survival. To investigate the function of NR4A1 in lymphomas, we overexpressed NR4A1 in several lymphoma cell lines. Overexpression of NR4A1 led to a higher proportion of lymphoma cells undergoing apoptosis. To test the tumor suppressor function of NR4A1 in vivo, the stable lentiviral-transduced SuDHL4 lymphoma cell line harboring an inducible NR4A1 construct was further investigated in xenografts. Induction of NR4A1 abrogated tumor growth in the NSG mice, in contrast to vector controls, which formed massive tumors. Our data suggest that NR4A1 has proapoptotic functions in aggressive lymphoma cells and define NR4A1 as a novel gene with tumor suppressor properties involved in lymphomagenesis.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Apoptosis - genetics
- Blotting, Western -
- Cell Line, Tumor -
- DNA-Binding Proteins - genetics
- Heterografts -
- Humans -
- Immunohistochemistry -
- Kaplan-Meier Estimate -
- Lymphoma, B-Cell - genetics
- Lymphoma, B-Cell - mortality
- Mice -
- Mice, Inbred NOD -
- Mice, SCID -
- Nuclear Receptor Subfamily 4, Group A, Member 1 - genetics
- Proportional Hazards Models -
- Receptors, Steroid - genetics
- Receptors, Thyroid Hormone - genetics