Smad signal and TGFbeta induced apoptosis in human lymphoma cells.
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.
Sebestyén
Anna
A
Ist Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, 1085 Budapest, Hungary. anna@korbl.sote.hu
Barna
Gábor
G
Nagy
Katalin
K
Jánosi
Judit
J
Paku
Sándor
S
Kohut
Eszter
E
Berczi
Lajos
L
Mihalik
Rudolf
R
Kopper
László
L
D017209:Apoptosis; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D051905:Smad6 Protein; D051906:Smad7 Protein; D015534:Trans-Activators / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; C497802:SMAD6 protein, human; C497806:SMAD7 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D051905:Smad6 Protein; D051906:Smad7 Protein; C508960:TGFB1 protein, human; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1