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

Richard Y. Liu,C. Fan,N. Olashaw,Xue Wang,K. Zuckerman

Published 1999 in Journal of Biological Chemistry

ABSTRACT

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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