Tumor necrosis factor-alpha-induced proliferation of human Mo7e leukemic cells occurs via activation of nuclear factor kappaB transcription factor.
Tumor necrosis factor-alpha (TNF-alpha) stimulates proliferation of Mo7e, CMK, HU-3, and M-MOK human leukemic cell lines. We report here the signal transduction pathway involved in TNF-alpha-induced Mo7e cell proliferation. Mo7e cells spontaneously die in the absence of growth factors, but treating the cells with interleukin (IL)-3, IL-6, thrombopoietin, granulocyte/macrophage colony-stimulating factor, or TNF-alpha promotes their survival and proliferation. Although most of these factors activate MAP kinase and Jun NH2-terminal kinase/signal transducer and activators of transcription signaling pathways, TNF-alpha fails to activate either pathway. When Mo7e cells were treated with TNF-alpha, nuclear factor kappaB (NF-kappaB) was activated transiently. The activated NF-kappaB consisted of heterodimers of p65 and p50 subunits. The degradation of IkappaBalpha coincided with activation of NF-kappaB in TNF-alpha-treated cells. To investigate the role of activated NF-kappaB in TNF-alpha-induced Mo7e proliferation, a cell-permeable peptide (SN50) carrying the nuclear localization sequence of p50 NF-kappaB was used to block nuclear translocation of activated NF-kappaB. Pretreating Mo7e cells with SN50 blocked TNF-alpha-induced nuclear translocation of NF-kappaB and inhibited TNF-alpha-induced Mo7e cell survival and proliferation. A mutant SN50 peptide did not affect TNF-alpha-induced Mo7e cell growth. SN50 had no effects on IL-3- or granulocyte/macrophage colony-stimulating factor-induced Mo7e cell proliferation. The results indicate that activation of NF-kappaB is involved in TNF-alpha-induced Mo7e cell survival and proliferation.
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007377:Interleukin-3 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D008894:Milk Proteins; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*