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TNF triggers mitogenic signals in NIH 3T3 cells but induces apoptosis when the cell cycle is blocked

René Rodríguez1, Victor M Campa, José Riera

  • 1Instituto Universitario de Oncología del Principado de Asturias and Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo, 33071 Oviedo, Spain.

European Cytokine Network
|November 13, 2007
PubMed

Insights

Tumor necrosis factor (TNF) triggers both cell growth and death signals in fibroblasts. In quiescent cells, TNF induces proliferation or apoptosis depending on serum availability, involving mitochondrial pathways.

Area of Science:

  • Cell Biology
  • Molecular Biology

Background:

  • Tumor necrosis factor (TNF) mediates diverse cellular responses, including apoptosis and proliferation.
  • The specific cellular outcome of TNF signaling is context-dependent, influenced by cell type and environmental conditions.

Purpose of the Study:

  • To investigate the dual role of TNF in triggering both growth and death signals in NIH 3T3 murine fibroblasts.
  • To elucidate the apoptotic pathway induced by TNF in arrested cells, focusing on the involvement of mitochondria and NF-kappaB.

Main Methods:

  • Utilizing serum deprivation to arrest NIH 3T3 cells in G(0).
  • Treating arrested and synchronized cells with TNF to observe proliferation and death.
  • Overexpressing Bcl-2 to assess the role of mitochondria in TNF-induced apoptosis.
  • Analyzing the activity of NF-kappaB in TNF-treated cells.

Main Results:

  • TNF induces cell cycle entry in approximately 50% of serum-deprived cells, while causing apoptosis in the remaining quiescent cells.
  • Serum presence prevents TNF-induced toxicity, suggesting cooperation for cell cycle progression.
  • TNF triggers apoptosis in cells arrested at the G(1)/S border, S, or M phases.
  • TNF-induced apoptosis in arrested cells is partially mediated by mitochondria, as indicated by Bcl-2 overexpression, and does not involve NF-kappaB inactivation.

Conclusions:

  • TNF exhibits a dual role in fibroblasts, promoting proliferation or apoptosis based on cell cycle status and serum availability.
  • The apoptotic pathway activated by TNF in arrested cells involves mitochondria but differs kinetically from other known TNF-induced apoptotic mechanisms.

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