TGF-β-induced growth inhibition in B-cell lymphoma correlates with Smad1-5 signalling and constitutively active p38 MAPKReport as inadecuate




TGF-β-induced growth inhibition in B-cell lymphoma correlates with Smad1-5 signalling and constitutively active p38 MAPK - Download this document for free, or read online. Document in PDF available to download.

BMC Immunology

, 11:57

First Online: 23 November 2010Received: 26 March 2010Accepted: 23 November 2010

Abstract

BackgroundCytokines of the transforming growth factor β TGF-β superfamily exert effects on proliferation, apoptosis and differentiation in various cell types. Cancer cells frequently acquire resistance to the anti-proliferative signals of TGF-β, which can be due to mutations in proteins of the signalling cascade. We compared the TGF-β-related signalling properties in B-cell lymphoma cell lines that were sensitive or resistant to TGF-β-induced anti-proliferative effects.

ResultsTGF-β sensitive cell lines expressed higher cell surface levels of the activin receptor-like kinase 5 Alk-5, a TGF-β receptor type 1. The expression levels of the other TGF-β and bone morphogenetic protein receptors were comparable in the different cell lines. TGF-β-induced phosphorylation of Smad2 was similar in TGF-β sensitive and resistant cell lines. In contrast, activation of Smad1-5 was restricted to cells that were sensitive to growth inhibition by TGF-β. Moreover, with activin A we detected limited anti-proliferative effects, strong phosphorylation of Smad2, but no Smad1-5 phosphorylation. Up-regulation of the TGF-β target genes Id1 and Pai-1 was identified in the TGF-β sensitive cell lines. Constitutive phosphorylation of MAPK p38 was restricted to the TGF-β sensitive cell lines. Inhibition of p38 MAPK led to reduced sensitivity to TGF-β.

ConclusionsWe suggest that phosphorylation of Smad1-5 is important for the anti-proliferative effects of TGF-β in B-cell lymphoma. Alk-5 was highly expressed in the sensitive cell lines, and might be important for signalling through Smad1-5. Our results indicate a role for p38 MAPK in the regulation of TGF-β-induced anti-proliferative effects.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2172-11-57 contains supplementary material, which is available to authorized users.

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Author: Maren Bakkebø - Kanutte Huse - Vera I Hilden - Erlend B Smeland - Morten P Oksvold

Source: https://link.springer.com/



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