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Smad signal and TGFbeta induced apoptosis in human lymphoma cells
Anna Sebestyén1, Gábor Barna, Katalin Nagy
1Ist Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, 1085 Budapest, Hungary. anna@korbl.sote.hu
Abstract:
Transforming growth factor beta1 (TGF beta1) has antiproliferative and/or apoptotic effect on lymphoid cells. In certain lymphomas exogenous TGF beta1 is able to induce apoptosis, however many lymphoid malignancies are resistant to the endogenous TGF beta1 production. We studied the expression and the activity of TGF beta1 signalling components in B cell lymphoma cell lines (e.g. HT 58 cells) and in isolated human peripheral mononuclear cells (PBMCs) from healthy individual's and B-CLL patient's blood. We found that all signal transducer Smads (Smad2,-3; Smad4) and at least one of the inhibitory Smads (Smad6,-7) were expressed in non-treated lymphoma cells, but the inhibitory Smads did not in normal/control PBMCs. However, after TGF beta1 treatment Smad6 disappeared, while the expression of Smad7 increased in HT 58 cells. The activity of Smad signals was proved by phosphorylation of Smad2, nuclear translocation of Smad2/3, and the increased expression of Smad-dependent gene, TIEG in TGF beta1 treated lymphoma cells. These results showed that Smad signaling is available in certain different human lymphoma cells, however ISmads expression could inhibit the signal transmission. This findings indicates that the lost sensitivity of lymphoma cells toward a physiological regulatory factor could be reversed.
Insights
Transforming growth factor beta1 (TGF-β1) can induce apoptosis in lymphomas. Inhibitory Smads in lymphoma cells block TGF-β1 signaling, but this resistance may be reversible.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Transforming growth factor beta1 (TGF-β1) exhibits antiproliferative and apoptotic effects on lymphoid cells.
- Many lymphoid malignancies display resistance to endogenous TGF-β1, despite its potential to induce apoptosis in certain lymphomas.
Purpose of the Study:
- To investigate the expression and activity of TGF-β1 signaling components in B cell lymphoma cell lines and human peripheral mononuclear cells (PBMCs).
- To understand the role of Smad proteins and inhibitory Smads (ISmads) in TGF-β1 resistance in lymphomas.
Main Methods:
- Analysis of Smad protein expression (Smad2, -3, -4, -6, -7) in B cell lymphoma cell lines (HT 58) and human PBMCs (healthy and B-CLL patients).
- Assessment of TGF-β1 signaling activity via Smad2 phosphorylation, nuclear translocation of Smad2/3, and TIEG gene expression following TGF-β1 treatment.
- Comparison of Smad expression profiles between lymphoma cells and normal PBMCs.
Main Results:
- Non-treated lymphoma cells expressed signal transducer Smads (Smad2, -3, -4) and inhibitory Smads (Smad6, -7), unlike normal PBMCs.
- TGF-β1 treatment led to the disappearance of Smad6 and increased Smad7 expression in HT 58 cells.
- Evidence of active Smad signaling in treated lymphoma cells, including Smad2 phosphorylation, nuclear translocation, and increased TIEG expression.
Conclusions:
- Smad signaling pathways are functional in certain human lymphoma cells.
- Inhibitory Smad expression can impede TGF-β1 signal transmission in lymphomas.
- The findings suggest that the diminished sensitivity of lymphoma cells to TGF-β1 may be reversible, offering potential therapeutic insights.
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