Format

Send to

Choose Destination
See comment in PubMed Commons below
Cancer Res. 2017 May 1;77(9):2375-2386. doi: 10.1158/0008-5472.CAN-16-2320. Epub 2017 Mar 1.

NR4A3 Suppresses Lymphomagenesis through Induction of Proapoptotic Genes.

Author information

1
Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. alexander.deutsch@medunigraz.at.
2
Center for Medical Research (ZMF), Medical University of Graz, Graz, Austria.
3
Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
4
Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
5
Institute of Molecular Biotechnology Graz University of Technology, Graz, Austria.
6
BioTechMed Omics Center Graz, Austria.
7
Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria.
8
Division of Bioinformatics, Biocenter Innsbruck, Innsbruck Medical University, Graz, Austria.
9
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.
10
Institute for Pathology, Medical University of Graz, Graz, Austria.

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.

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center