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

doi:10.1158/0008-5472.CAN-16-2320

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

Institut für Molekulare Biotechnologie (6550)

Publikation: Beitrag in einer Fachzeitschrift › Artikel › Begutachtung

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.

Originalsprache	englisch
Seiten (von - bis)	2375-2386
Fachzeitschrift	Cancer Research
Jahrgang	77
Ausgabenummer	9
DOIs	https://doi.org/10.1158/0008-5472.CAN-16-2320
Publikationsstatus	Veröffentlicht - 1 Mai 2017

Fields of Expertise

Human- & Biotechnology
Information, Communication & Computing

Treatment code (Nähere Zuordnung)

Basic - Fundamental (Grundlagenforschung)
Experimental

Kooperationen

BioTechMed-Graz

UN SDGs

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10.1158/0008-5472.CAN-16-2320

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Deutsch, A. J. A., Rinner, B., Pichler, M., Prochazka, K., Pansy, K., Bischof, M., Fechter, K., Hatzl, S., Feichtinger, J., Wenzl, K., Frisch, M.-T., Stiegelbauer, V., Prokesch, A., Krogsdam, A., Sill, H., Thallinger, G. G., Greinix, H. T., Wang, C., Beham-Schmid, C., & 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

Deutsch, AJA, Rinner, B, Pichler, M, Prochazka, K, Pansy, K, Bischof, M, Fechter, K, Hatzl, S, Feichtinger, J, Wenzl, K, Frisch, M-T, Stiegelbauer, V, Prokesch, A, Krogsdam, A, Sill, H, Thallinger, GG, Greinix, HT, Wang, C, Beham-Schmid, C & Neumeister, P 2017, 'NR4A3 Suppresses Lymphomagenesis through Induction of Proapoptotic Genes', Cancer Research, Jg. 77, Nr. 9, S. 2375-2386. https://doi.org/10.1158/0008-5472.CAN-16-2320

@article{8460b089a7e24db48b297fcb639616bf,

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. {\textcopyright}2017 AACR.",

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",

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

note = "{\textcopyright}2017 American Association for Cancer Research.",

year = "2017",

month = may,

day = "1",

doi = "10.1158/0008-5472.CAN-16-2320",

language = "English",

volume = "77",

pages = "2375--2386",

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publisher = "American Association for Cancer Research",

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TY - JOUR

T1 - NR4A3 Suppresses Lymphomagenesis through Induction of Proapoptotic Genes

AU - Deutsch, Alexander J A

AU - Rinner, Beate

AU - Pichler, Martin

AU - Prochazka, Katharina

AU - Pansy, Katrin

AU - Bischof, Marco

AU - Fechter, Karoline

AU - Hatzl, Stefan

AU - Feichtinger, Julia

AU - Wenzl, Kerstin

AU - Frisch, Marie-Therese

AU - Stiegelbauer, Verena

AU - Prokesch, Andreas

AU - Krogsdam, Anne

AU - Sill, Heinz

AU - Thallinger, Gerhard G

AU - Greinix, Hildegard T

AU - Wang, Chenguang

AU - Beham-Schmid, Christine

AU - Neumeister, Peter

PY - 2017/5/1

Y1 - 2017/5/1

N2 - 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.

AB - 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.

KW - Animals

KW - Apoptosis

KW - Carcinogenesis

KW - Cell Line, Tumor

KW - Cell Proliferation

KW - DNA-Binding Proteins

KW - Disease-Free Survival

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Kaplan-Meier Estimate

KW - Lymphoma

KW - Male

KW - Mice

KW - Receptors, Steroid

KW - Receptors, Thyroid Hormone

KW - Xenograft Model Antitumor Assays

KW - Journal Article

U2 - 10.1158/0008-5472.CAN-16-2320

DO - 10.1158/0008-5472.CAN-16-2320

M3 - Article

C2 - 28249906

SN - 1538-7445

VL - 77

SP - 2375

EP - 2386

JO - Cancer Research

JF - Cancer Research

IS - 9

ER -

NR4A3 Suppresses Lymphomagenesis through Induction of Proapoptotic Genes

Abstract

Fields of Expertise

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UN SDGs

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