title: NR4A3 Suppresses Lymphomagenesis through Induction of Proapoptotic Genes.
abstract: Nuclear orphan receptor NR4A1 exerts an essential tumor suppressor function in aggressive lymphomas. In this study, we investigated the hypothesized contribution of the related NR4A family member NR4A3 to lymphomagenesis. In aggressive lymphoma patients, low expression of NR4A3 was associated with poor survival. Ectopic expression or pharmacological activation of NR4A3 in lymphoma cell lines led to a significantly higher proportion of apoptotic cells. In a mouse NSG xenograft model of lymphoma (stably transduced SuDHL4 cells), NR4A3 expression abrogated tumor growth, compared with vector control and uninduced cells that formed massive tumors. Transcript analysis of four different aggressive lymphoma cell lines overexpressing either NR4A3 or NR4A1 revealed that apoptosis was driven similarly by induction of BAK, Puma, BIK, BIM, BID, and Trail. Overall, our results showed that NR4A3 possesses robust tumor suppressor functions of similar impact to NR4A1 in aggressive lymphomas.Cancer Res; 77(9); 2375-86. ©2017 AACR.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. alexander.deutsch@medunigraz.at.
authors.forename: Alexander J A
authors.initials: AJA
authors.lastname: Deutsch
authors.affiliation: Center for Medical Research (ZMF), Medical University of Graz, Graz, Austria.
authors.forename: Beate
authors.initials: B
authors.lastname: Rinner
authors.affiliation: Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Pichler
authors.affiliation: Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Prochazka
authors.affiliation: Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Katrin
authors.initials: K
authors.lastname: Pansy
authors.affiliation: Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Marco
authors.initials: M
authors.lastname: Bischof
authors.affiliation: Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Karoline
authors.initials: K
authors.lastname: Fechter
authors.affiliation: Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hatzl
authors.affiliation: Institute of Molecular Biotechnology Graz University of Technology, Graz, Austria.|BioTechMed Omics Center Graz, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Feichtinger
authors.affiliation: Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wenzl
authors.affiliation: Center for Medical Research (ZMF), Medical University of Graz, Graz, Austria.
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Frisch
authors.affiliation: Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Verena
authors.initials: V
authors.lastname: Stiegelbauer
authors.affiliation: Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Prokesch
authors.affiliation: Division of Bioinformatics, Biocenter Innsbruck, Innsbruck Medical University, Graz, Austria.
authors.forename: Anne
authors.initials: A
authors.lastname: Krogsdam
authors.affiliation: Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Sill
authors.affiliation: Institute of Molecular Biotechnology Graz University of Technology, Graz, Austria.|BioTechMed Omics Center Graz, Austria.
authors.forename: Gerhard G
authors.initials: GG
authors.lastname: Thallinger
authors.affiliation: Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Hildegard T
authors.initials: HT
authors.lastname: Greinix
authors.affiliation: Key Laboratory of Tianjin Radiation and Molecular Nuclear Medicine; Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute for Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Beham-Schmid
authors.affiliation: Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Neumeister
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008223:Lymphoma / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D011987:Receptors, Steroid / Q000096:biosynthesis / Q000235:genetics*; D011988:Receptors, Thyroid Hormone / Q000096:biosynthesis / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D004268:DNA-Binding Proteins; C490412:NR4A3 protein, human; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone