CELL BIOLOGY AND METABOLISM
Tumor Necrosis Factor-α-induced Proliferation of Human Mo7e Leukemic Cells Occurs via Activation of Nuclear Factor κB Transcription Factor*

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Tumor necrosis factor-α (TNF-α) stimulates proliferation of Mo7e, CMK, HU-3, and M-MOK human leukemic cell lines. We report here the signal transduction pathway involved in TNF-α-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-α 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-α fails to activate either pathway. When Mo7e cells were treated with TNF-α, nuclear factor κB (NF-κB) was activated transiently. The activated NF-κB consisted of heterodimers of p65 and p50 subunits. The degradation of IκBα coincided with activation of NF-κB in TNF-α-treated cells. To investigate the role of activated NF-κB in TNF-α-induced Mo7e proliferation, a cell-permeable peptide (SN50) carrying the nuclear localization sequence of p50 NF-κB was used to block nuclear translocation of activated NF-κB. Pretreating Mo7e cells with SN50 blocked TNF-α-induced nuclear translocation of NF-κB and inhibited TNF-α-induced Mo7e cell survival and proliferation. A mutant SN50 peptide did not affect TNF-α-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-κB is involved in TNF-α-induced Mo7e cell survival and proliferation.

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This work was supported in part by National Institutes of Health NCI Grants CA56072 and P30 CA76292 and by the Flow Cytometry Core Facility at the H. Lee Moffitt Cancer Center and Research Institute.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.