PMID- 15927846 OWN - NLM STAT- MEDLINE DCOM- 20051115 LR - 20061115 IS - 1043-4666 (Print) IS - 1043-4666 (Linking) VI - 30 IP - 5 DP - 2005 Jun 7 TI - Smad signal and TGFbeta induced apoptosis in human lymphoma cells. PG - 228-35 AB - 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. FAU - Sebestyen, Anna AU - Sebestyen A AD - Ist Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, 1085 Budapest, Hungary. anna@korbl.sote.hu FAU - Barna, Gabor AU - Barna G FAU - Nagy, Katalin AU - Nagy K FAU - Janosi, Judit AU - Janosi J FAU - Paku, Sandor AU - Paku S FAU - Kohut, Eszter AU - Kohut E FAU - Berczi, Lajos AU - Berczi L FAU - Mihalik, Rudolf AU - Mihalik R FAU - Kopper, Laszlo AU - Kopper L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050317 PL - England TA - Cytokine JT - Cytokine JID - 9005353 RN - 0 (DNA-Binding Proteins) RN - 0 (RNA, Messenger) RN - 0 (SMAD2 protein, human) RN - 0 (SMAD3 protein, human) RN - 0 (SMAD4 protein, human) RN - 0 (SMAD6 protein, human) RN - 0 (SMAD7 protein, human) RN - 0 (Smad2 Protein) RN - 0 (Smad3 Protein) RN - 0 (Smad4 Protein) RN - 0 (Smad6 Protein) RN - 0 (Smad7 Protein) RN - 0 (TGFB1 protein, human) RN - 0 (Trans-Activators) RN - 0 (Transforming Growth Factor beta) RN - 0 (Transforming Growth Factor beta1) SB - IM MH - *Apoptosis MH - Cell Line, Tumor MH - DNA-Binding Proteins/*metabolism MH - Humans MH - Lymphoma/genetics/*metabolism/*pathology MH - RNA, Messenger/genetics/metabolism MH - *Signal Transduction MH - Smad2 Protein MH - Smad3 Protein MH - Smad4 Protein MH - Smad6 Protein MH - Smad7 Protein MH - Trans-Activators/*metabolism MH - Transforming Growth Factor beta/genetics/*metabolism MH - Transforming Growth Factor beta1 EDAT- 2005/06/02 09:00 MHDA- 2005/11/16 09:00 CRDT- 2005/06/02 09:00 PHST- 2004/02/23 00:00 [received] PHST- 2004/10/26 00:00 [revised] PHST- 2005/01/25 00:00 [accepted] PHST- 2005/06/02 09:00 [pubmed] PHST- 2005/11/16 09:00 [medline] PHST- 2005/06/02 09:00 [entrez] AID - S1043-4666(05)00046-3 [pii] AID - 10.1016/j.cyto.2005.01.013 [doi] PST - ppublish SO - Cytokine. 2005 Jun 7;30(5):228-35. doi: 10.1016/j.cyto.2005.01.013. Epub 2005 Mar 17.