NR4A3 Suppresses Lymphomagenesis through Induction of Proapoptotic Genes

Alexander J A Deutsch, Beate Rinner, Martin Pichler, Katharina Prochazka, Katrin Pansy, Marco Bischof, Karoline Fechter, Stefan Hatzl, Julia Feichtinger, Kerstin Wenzl, Marie-Therese Frisch, Verena Stiegelbauer, Andreas Prokesch, Anne Krogsdam, Heinz Sill, Gerhard G Thallinger, Hildegard T Greinix, Chenguang Wang, Christine Beham-Schmid, Peter Neumeister

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)2375-2386
JournalCancer Research
Volume77
Issue number9
DOIs
Publication statusPublished - 1 May 2017

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Keywords

  • Animals
  • Apoptosis
  • Carcinogenesis
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA-Binding Proteins
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Lymphoma
  • Male
  • Mice
  • Receptors, Steroid
  • Receptors, Thyroid Hormone
  • Xenograft Model Antitumor Assays
  • Journal Article

Fields of Expertise

  • Human- & Biotechnology
  • Information, Communication & Computing

Treatment code (Nähere Zuordnung)

  • Basic - Fundamental (Grundlagenforschung)
  • Experimental

Cooperations

  • BioTechMed-Graz

Cite this

Deutsch, A. J. A., Rinner, B., Pichler, M., Prochazka, K., Pansy, K., Bischof, M., ... Neumeister, P. (2017). NR4A3 Suppresses Lymphomagenesis through Induction of Proapoptotic Genes. Cancer Research, 77(9), 2375-2386. https://doi.org/10.1158/0008-5472.CAN-16-2320