NR4A3 Suppresses Lymphomagenesis through Induction of Proapoptotic Genes
Autor: | Hildegard Greinix, Alexander Deutsch, Christine Beham-Schmid, Peter Neumeister, Marco Bischof, Chenguang Wang, Heinz Sill, Anne Krogsdam, Karoline Fechter, Katharina T. Prochazka, Gerhard G. Thallinger, Marie-Therese Frisch, Martin Pichler, Julia Feichtinger, Andreas Prokesch, Stefan Hatzl, Verena Stiegelbauer, Beate Rinner, Katrin Pansy, Kerstin Wenzl |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Male Cancer Research Receptors Steroid Lymphoma Carcinogenesis Aggressive lymphoma Apoptosis Kaplan-Meier Estimate medicine.disease_cause Disease-Free Survival 03 medical and health sciences Mice 0302 clinical medicine hemic and lymphatic diseases Puma Cell Line Tumor medicine Animals Humans Cell Proliferation Orphan receptor Receptors Thyroid Hormone biology Cell growth medicine.disease biology.organism_classification Xenograft Model Antitumor Assays DNA-Binding Proteins Gene Expression Regulation Neoplastic 030104 developmental biology Oncology 030220 oncology & carcinogenesis Immunology Cancer research Ectopic expression Female |
Zdroj: | Cancer research. 77(9) |
ISSN: | 1538-7445 |
Popis: | 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. |
Databáze: | OpenAIRE |
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