Related Experiment Video

Updated: Jul 16, 2026

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

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

Young-Rae Lee1, Hong-Nu Yu, Eun-Mi Noh

  • 1Department of Biochemistry, Chonbuk National University Medical School, Jeonju 561-180, Korea.

Experimental & Molecular Medicine
|March 6, 2007
PubMed

Insights

Tumor Necrosis Factor-alpha (TNF-alpha) upregulates PTEN expression in human leukemic cells. This occurs through the activation of the NF-kappaB pathway, contrary to previous findings in colon cells.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Tumor Necrosis Factor-alpha (TNF-alpha) is a cytokine involved in apoptosis, inflammation, and immunity.
  • Phosphatase and Tensin homolog (PTEN) is a tumor suppressor protein regulating cell growth, proliferation, migration, and differentiation.
  • Previous studies indicated TNF-alpha downregulates PTEN via the NF-kappaB pathway in HT-29 colon cells.

Purpose of the Study:

  • To investigate the relationship between TNF-alpha and PTEN expression in human leukemic cells.
  • To elucidate the specific molecular pathway involved in TNF-alpha's effect on PTEN.

Main Methods:

  • Treatment of HL-60 human leukemic cells with TNF-alpha.
  • Assessment of PTEN expression levels in a time- and dose-dependent manner.
  • Inhibition of the NF-kappaB pathway using p65 antisense phosphorothioate oligonucleotide and pyrrolidine dithiocarbamate.
  • Analysis of NF-kappaB activation by examining the nuclear translocation of the p65 subunit.

Main Results:

  • TNF-alpha significantly increased PTEN expression in HL-60 cells.
  • The observed increase in PTEN was dose- and time-dependent.
  • Inhibition of NF-kappaB activation abolished the TNF-alpha-induced upregulation of PTEN.
  • TNF-alpha treatment led to the activation of NF-kappaB, confirmed by p65 nuclear translocation.

Conclusions:

  • TNF-alpha induces the upregulation of PTEN expression in human leukemic cells.
  • This upregulation is mediated by the activation of the NF-kappaB signaling pathway.
  • The findings present an opposite effect of TNF-alpha on PTEN compared to previous observations in non-leukemic cells.

More Related Videos

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...