Exp Mol Med.  2007 Feb;39(1):121-127.

TNF-alpha upregulates PTEN via NF-kappaB signaling pathways in human leukemic cells

  • 1Department of Biochemistry, Chonbuk National University Medical School, Jeonju 561-180, Korea. jsukim@moak.chonbuk.ac.kr
  • 2Department of Microbiology and Immunology, Chonbuk National University Medical School, Jeonju 561-180, Korea.
  • 3Division of Animal Science and Resources, Research Center for Transgenic Cloned Pigs, Chungnam National University, Daejeon 305-764, Korea.
  • 4Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 340-702, Korea.


TNF-alpha 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-alpha has been known to downregulate PTEN via NF-kappaB pathway in the human colon cell line, HT-29. However, here we show the opposite finding that TNF-alpha upregulates PTEN via activation of NF-kappaB in human leukemic cells. TNF-alpha increased PTEN expression at HL-60 cells in a time- and dose-dependent manner, but the response was abolished by disruption of NF-kappaB with p65 anisense phosphorothioate oligonucleotide or pyrrolidine dithiocarbamate. We found that TNF-alpha activated the NF-kappaB pathways, evidenced by the translocation of p65 to the nucleus in TNF-alpha-treated cells. We conclude that TNF-alpha induces upregulation of PTEN expression through NF-kappaB activation in human leukemic cells.


leukemia; NF-kappaB; PTEN phosphohydrolase; tumor necrosis factor-alpha

MeSH Terms

Up-Regulation/*drug effects
Tumor Necrosis Factor-alpha/*pharmacology
Signal Transduction/*drug effects
PTEN Phosphohydrolase/genetics/*metabolism
NF-kappa B/genetics/*metabolism
Gene Expression
Cell Line, Tumor
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