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The antimitogenic action of tumor necrosis factor is associated with increased AP-1/c-jun proto-oncogene

V M Dixit1, R M Marks, V Sarma

  • 1Department of Pathology, University of Michigan School of Medicine, Ann Arbor 48109.

The Journal of Biological Chemistry
|October 5, 1989
PubMed

Insights

Tumor necrosis factor alpha (TNF) induces the AP-1/c-jun transcription factor in endothelial cells, contributing to its anti-cancer effects. This molecular response is key to TNF

Area of Science:

  • Molecular biology
  • Cellular biology
  • Oncology

Background:

  • Tumor necrosis factor alpha (TNF) exhibits anti-cancer properties by affecting tumor vasculature.
  • TNF induces procoagulant molecules on endothelial cells, leading to microthrombi and tumor anoxia.
  • TNF also acts as an antimitotic agent for endothelial cells.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying TNF's diverse effects on endothelial cells.
  • To identify specific gene expression changes induced by TNF in human umbilical vein endothelial (HUVE) cells.

Main Methods:

  • Differential screening of a cDNA library from TNF and cycloheximide-treated HUVE cells.
  • Analysis of gene expression, specifically focusing on transcription factors.

Main Results:

  • AP-1/c-jun, a transcription factor and proto-oncogene, was identified as a key gene induced by TNF.
  • TNF-induced AP-1/c-jun expression occurs primarily at the transcriptional level.
  • TNF did not induce c-myc or c-fos transcripts, suggesting distinct molecular responses to mitogenic and antimitogenic stimuli.

Conclusions:

  • AP-1/c-jun transcript induction is an early molecular event in TNF-treated HUVE cells.
  • Distinct, yet overlapping, molecular responses are triggered by mitogenic and antimitogenic signals.
  • The coordinate expression of AP-1/c-jun and c-fos is not essential for cellular responses to growth factors or TNF.

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