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

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 IFNalpha-mediated growth inhibition without affecting Stat3 activation, growth, and apoptosis, and (iv) inhibition of SOCS-3 by a dominant negative Stat3 (Stat3D) increases the IFNalpha-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 IFNalpha. Unlike SOCS-1, SOCS-3 is therefore not a tumour suppressor but rather a protector of tumour cells.

journal_name

Leukemia

journal_title

Leukemia

authors

Brender C,Lovato P,Sommer VH,Woetmann A,Mathiesen AM,Geisler C,Wasik M,Ødum N

doi

10.1038/sj.leu.2403610

subject

Has Abstract

pub_date

2005-02-01 00:00:00

pages

209-13

issue

2

eissn

0887-6924

issn

1476-5551

pii

2403610

journal_volume

19

pub_type

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