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T-Cell Lymphoma

Constitutive SOCS-3 expression protects T-cell lymphoma against growth inhibition by IFNα

Leukemia volume 19, pages 209–213 (2005)Cite this article

Abstract

Signal transducer and activator of transcription (Stat)3 is constitutively activated in cutaneous T-cell lymphoma (CTCL), where it protects tumour cells against apoptosis. The constitutive activation of Stat3 leads to a constitutive expression of suppressor of cytokine signalling (SOCS)-3. In healthy cells, SOCS-3 is transiently expressed following cytokine stimulation and functions as a negative feedback inhibitor of the Stat3-activating kinases. Here, we attempt to resolve the apparent paradox of a simultaneous SOCS-3 expression and Stat3 activation in the same cells. We show that (i) SOCS-3 expression in tumour cells is equal to or higher than in cytokine-stimulated nonmalignant T cells, (ii) SOCS-3 is not mutated in CTCL, (iii) overexpression of SOCS-3 blocks IFNα-mediated growth inhibition without affecting Stat3 activation, growth, and apoptosis, and (iv) inhibition of SOCS-3 by a dominant negative Stat3 (Stat3D) increases the IFNα-mediated growth inhibition. Taken together, these data show that SOCS-3 does not inhibit Stat3 activation, growth, and survival in CTCL. In contrast, SOCS3 protects tumour cells against growth inhibition by IFNα. Unlike SOCS-1, SOCS-3 is therefore not a tumour suppressor but rather a protector of tumour cells.

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Acknowledgements

This work was supported by the University of Copenhagen PhD programme (for CB and AW), The Danish Colitis Crohn Foundation, The Danish Research Councils, Danish Biotechnological Centre for Cellular Communication, Novo Nordic Foundation, Becketts Fond, Danish Medical Association Research Foundation, The Danish Cancer Research Foundation (Dansk Kræftsforsknings Fond), The Danish Cancer Society, Ingeborg and Leo Dannins Foundation, The Lundbeck Foundation, Gerda and Aage Haensch's Foundation, Danish Rheumatism Association, National Cancer Institute and NIH R01-CA89194 grant (for MW). PL is the recipient of a fellowship from Alfred Benzon Foundation.

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  1. C Brender and P Lovato: Both these authors contributed equally to this work

Authors and Affiliations

  1. Institute of Medical Microbiology and Immunology, Institute of Molecular Biology, University of Copenhagen, Denmark

    C Brender, P Lovato, V H Sommer, A Woetmann, A-M Mathiesen, C Geisler & N Ødum

  2. Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA

    M Wasik

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Brender, C., Lovato, P., Sommer, V. et al. Constitutive SOCS-3 expression protects T-cell lymphoma against growth inhibition by IFNα. Leukemia 19, 209–213 (2005). https://doi.org/10.1038/sj.leu.2403610

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