Signal transduction in anaplastic large cell lymphoma cells (ALCL) mediated by the tumor necrosis factor receptor CD30.
Expression of the cytokine receptor CD30 is a characteristic feature of anaplastic large cell lymphoma (ALCL). Reports regarding CD30-mediated signaling in ALCL cells are highly controversial, especially with respect to the regulation of cell survival. In this study, we stimulated 6 ALCL-derived cell lines with immobilized anti-CD30 antibody. CD30-induced cell death was investigated by Western blot and FACS analysis. CD30-dependent cell proliferation and activation was analyzed by applying the trypan blue exclusion method and a luciferase-based ATP assay. The expression of cell cycle relevant proteins and the activation of mitogen-activated protein (MAP) kinases were also examined. We demonstrated that activation of CD30 did not lead to the cleavage of pro-caspase-3. FACS analysis confirmed that in all examined cells cell death was not mediated by CD30. Cell growth was strongly inhibited in 2 of the 6 cell lines and restrained cell growth was accompanied by expression of the cell cycle inhibitor p21(WAF1/CIP1). Furthermore, stimulation of CD30 led to the activation of the p38 MAP kinase but not of the extracellular signal-regulated kinase (ERK) or the jun N-terminal kinase (JNK). Interestingly, activation of CD30 induced a strong synergistic reduction of cell activity, if the p38 MAP kinase activity was blocked by SB203580. The aim of the study was to elucidate CD30-induced signaling in different ALCL-cells. Our results suggest that CD30-mediated apoptosis is not a common feature in this cell type and that p38 MAP kinase is involved in CD30-mediated singal transduction.
Department of Internal Medicine II, University of Ulm, Ulm, Germany. christof74@gmx.de
Christof
C
Schneider
Dagmar
D
Stöhr
Hartmut
H
Merz
Gabriele
G
Hübinger
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D017730:Ki-1 Antigen / Q000276:immunology / Q000502:physiology*; D017728:Lymphoma, Large-Cell, Anaplastic / Q000473:pathology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000911:Antibodies, Monoclonal; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017730:Ki-1 Antigen; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases