Selective effect of tumor necrosis factor on transformed versus nontransformed cells: nonselective signal recognition

A Schulz1, G Bauer

  • 1Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene Universität Freiburg, D-79104 Freiburg, Germany.

Anticancer Research
|December 29, 2000
PubMed

Insights

Tumor necrosis factor (TNF) triggers cell death by reducing survival factors in transformed cells. Nontransformed cells resist TNF-induced apoptosis due to higher initial survival factor levels.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Endogenous survival factors regulate apoptosis.
  • Transformed cells have lower survival factor levels than nontransformed cells.
  • Tumor necrosis factor (TNF) can induce apoptosis.

Purpose of the Study:

  • To investigate the differential response of transformed and nontransformed fibroblasts to TNF treatment.
  • To elucidate the role of endogenous survival factors in TNF-induced apoptosis.
  • To explain the sensitizing effect of cycloheximide on TNF-alpha-induced apoptosis.

Main Methods:

  • Cell culture of transformed and nontransformed fibroblasts.
  • Treatment with TNF and cycloheximide.
  • Quantification of endogenous survival factors.
  • Assessment of apoptosis induction.

Main Results:

  • TNF treatment down-modulates endogenous survival factors in both cell types.
  • Transformed cells undergo apoptosis due to sufficient down-modulation of survival factors.
  • Nontransformed cells are protected from apoptosis by higher initial survival factor concentrations.
  • TNF signaling perception is similar, but regulatory setup differs quantitatively.

Conclusions:

  • Differential sensitivity to TNF-induced apoptosis is determined by the quantitative levels of endogenous survival factors.
  • Lower initial survival factor concentrations in transformed cells predispose them to TNF-induced cell death.
  • Cycloheximide sensitizes cells to TNF-alpha by further inhibiting survival factor production.

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