Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Wenzl, K; Troppan, K; Neumeister, P; Deutsch, AJ.
The nuclear orphan receptor NR4A1 and NR4A3 as tumor suppressors in hematologic neoplasms.
Curr Drug Targets. 2015; 16(1):38-46
Doi: 10.2174/1389450115666141120112818
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Deutsch Alexander
- Wenzl Kerstin
- Co-Autor*innen der Med Uni Graz
- Neumeister Peter
- Prochazka Katharina
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- Abstract:
- NR4A1 (Nur77) belongs together with NR4A2 (Nurr1) and NR4A3 (NOR-1) to the nuclear orphan receptors of the NR4A-family. Their activation is generally short lived, the cellular outcome is a stimulus- and cell context-dependent differential activation of NR4A target genes that regulate cell cycle, apoptosis, inflammation, atherogenesis, metabolism, DNA repair and tumorigenesis. NR4A1 and NR4A3 were identified to function as tumor suppressors in acute myeloid leukemia (AML). Deletion of both nuclear receptors led to rapid development of AML in mice. Loss of NR4A1 and NR4A3 was a common feature in human AML patients. Additionally, NR4A1 and NR4A3 hypoallelic mice - mice with a reduced NR4A1 and NR4A3 expression - develop a chronic myeloid malignancy that recapitulates the pathological features of myelodysplastic/ myeloproliferative neoplasms with progression to AML in rare cases. Recently, a reduced NR4A1 and NR4A3 expression was described in aggressive lymphomas and low NR4A1 expression was associated with poor overall survival. Overexpression of NR4A1 in aggressive lymphoma cells led to induction of apoptosis and abrogated tumor growth in a xenograft mouse model. Recently, it was shown that NR4A inducing agents or NR4A agonist possess/induce apoptotic effects in AML and lymphoma cells. Due to this fact and the growing number of NR4A1 and NR4A3 inducing agents and NR4A agonists, both receptors represent new targets for anti tumor therapy.
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- Animals -
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- Cell Cycle - drug effects
- DNA-Binding Proteins - genetics
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- Gene Expression Regulation, Neoplastic - drug effects
- Hematologic Neoplasms - drug therapy
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- Mice -
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- Neoplasms, Experimental - drug therapy
- Neoplasms, Experimental - genetics
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- Nuclear Receptor Subfamily 4, Group A, Member 1 - genetics
- Nuclear Receptor Subfamily 4, Group A, Member 1 - metabolism
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- Receptors, Thyroid Hormone - genetics
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- Find related publications in this database (Keywords)
- AML
- apoptosis
- cell cycle arrest
- lymphoma
- NR4A
- therapeutic target
- tumor suppressor