TGF beta 1 induces caspase-dependent but death-receptor independent apoptosis in lymphoid cells.
Transforming growth factor beta 1 (TGF beta 1) is an antiproliferative and proapoptotic cytokine for normal B-cells, however many B-cell lymphomas have lost their response to TGF beta 1. The aim of this study was to identify the sequence of events in apoptosis induced by TGF beta 1 in an EBV negative, human B-cell lymphoma line (HT58). The proportion of apoptotic cells increased gradually (up to 72 hr) at an optimal dose range of 0.5-1.0 ng/ml. The induced cell death required the action of downstream caspases. Caspase activation was accompanied by an increase in the permeability of mitochondrial membranes, but there was no change in the expression of certain members of Bcl-2 family (Bcl-2, Bax, Bcl-XL). Similarly, none of the death receptors or ligands were involved in apoptosis induction. Further study will include the participation of TGF beta 1 target genes in the pore formation of mitochondrial membranes and/or the elimination of a putative survival signal.
Tótth
A
A
Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
Sebestyén
A
A
Barna
G
G
Nagy
K
K
Göndör
A
A
Bocsi
J
J
Mihalik
R
R
Peták
I
I
Houghton
J
J
Kopper
L
L
D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D058851:GPI-Linked Proteins; D006801:Humans; D008214:Lymphocytes / Q000166:cytology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured; D053319:Tumor Necrosis Factor Decoy Receptors
D058851:GPI-Linked Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053320:Receptors, Tumor Necrosis Factor, Member 10c; C508960:TGFB1 protein, human; C505639:TNFRSF10B protein, human; C108661:TNFRSF10C protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053319:Tumor Necrosis Factor Decoy Receptors; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases