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TNF-α plays a variety of biological functions such as apoptosis, inflammation and immunity. PTEN also has various cellular function including cell growth, proliferation, migration and differentiation. Thus, possible relationships between the two molecules are suggested. TNF-α has been known to down-regulate PTEN via NF-κB pathway in the human colon cell line, HT-29. However, here we show the opposite finding that TNF-α upregulates PTEN via activation of NF-κ α increased PTEN expression at HL-60 cells in a time- and dose-dependent manner, but the response was abolished by disruption of NF-κB with p65 anisense phosphorothioate oligonucleotide or pyrrolidine dithiocarbamate. We found that TNF-α activated the NF-κB pathways, evidenced by the translocation of p65 to the nucleus in TNF-α-treated cells. We conclude that TNF-α induces upregulation of PTEN expression through NF-κB activation in human leukemic cells.