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

Publikation: Beitrag in einer FachzeitschriftArtikelForschungBegutachtung

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.

Originalspracheenglisch
Seiten (von - bis)2375-2386
FachzeitschriftCancer Research
Jahrgang77
Ausgabenummer9
DOIs
PublikationsstatusVeröffentlicht - 1 Mai 2017

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Lymphoma
Genes
Neoplasms
Nuclear Receptor Subfamily 4, Group A, Member 1
Puma
Cell Line
Heterografts
Pharmacology
Apoptosis
Survival
Growth

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    Fields of Expertise

    • Human- & Biotechnology
    • Information, Communication & Computing

    Treatment code (Nähere Zuordnung)

    • Basic - Fundamental (Grundlagenforschung)
    • Experimental

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    • BioTechMed-Graz

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    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

    NR4A3 Suppresses Lymphomagenesis through Induction of Proapoptotic Genes. / Deutsch, Alexander J A; Rinner, Beate; Pichler, Martin; Prochazka, Katharina; Pansy, Katrin; Bischof, Marco; Fechter, Karoline; Hatzl, Stefan; Feichtinger, Julia; Wenzl, Kerstin; Frisch, Marie-Therese; Stiegelbauer, Verena; Prokesch, Andreas; Krogsdam, Anne; Sill, Heinz; Thallinger, Gerhard G; Greinix, Hildegard T; Wang, Chenguang; Beham-Schmid, Christine; Neumeister, Peter.

    in: Cancer Research, Jahrgang 77, Nr. 9, 01.05.2017, S. 2375-2386.

    Publikation: Beitrag in einer FachzeitschriftArtikelForschungBegutachtung

    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
    Deutsch AJA, Rinner B, Pichler M, Prochazka K, Pansy K, Bischof M et al. NR4A3 Suppresses Lymphomagenesis through Induction of Proapoptotic Genes. Cancer Research. 2017 Mai 1;77(9):2375-2386. https://doi.org/10.1158/0008-5472.CAN-16-2320
    Deutsch, Alexander J A ; Rinner, Beate ; Pichler, Martin ; Prochazka, Katharina ; Pansy, Katrin ; Bischof, Marco ; Fechter, Karoline ; Hatzl, Stefan ; Feichtinger, Julia ; Wenzl, Kerstin ; Frisch, Marie-Therese ; Stiegelbauer, Verena ; Prokesch, Andreas ; Krogsdam, Anne ; Sill, Heinz ; Thallinger, Gerhard G ; Greinix, Hildegard T ; Wang, Chenguang ; Beham-Schmid, Christine ; Neumeister, Peter. / NR4A3 Suppresses Lymphomagenesis through Induction of Proapoptotic Genes. in: Cancer Research. 2017 ; Jahrgang 77, Nr. 9. S. 2375-2386.
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    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. {\circledC}2017 AACR.",
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    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

    N1 - ©2017 American Association for Cancer Research.

    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

    VL - 77

    SP - 2375

    EP - 2386

    JO - Cancer Research

    JF - Cancer Research

    SN - 0008-5472

    IS - 9

    ER -