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Oncogenic transformation increases the sensitivity for apoptosis induction by inhibitors of macromolecular synthesis

J Hanusch1, A Schwieger, C Sers

  • 1Abteilung Virologie, Institut fur Medizinische Mikrobiologie und Hygiene, Universitat Freiburg, Germany.

International Journal of Oncology
|June 15, 2000
PubMed

Insights

Fibroblasts undergo apoptosis when RNA or protein synthesis is inhibited, revealing a balance between cell death machinery and short-lived survival factors. Oncogene transformation decreases these survival factors, increasing apoptosis sensitivity.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • Apoptosis, or programmed cell death, is crucial for tissue homeostasis.
  • Fibroblasts possess a latent apoptosis mechanism regulated by short-lived endogenous survival factors.
  • Inhibiting macromolecular synthesis triggers apoptosis, with the delay indicating survival factor levels.

Purpose of the Study:

  • To investigate the role of endogenous survival factors in fibroblast apoptosis.
  • To determine how oncogene expression affects apoptosis sensitivity and survival factor levels.
  • To establish a method for estimating endogenous survival factor concentration.

Main Methods:

  • Inhibition of RNA and protein synthesis in rat fibroblasts.
  • Assessment of apoptosis induction time as a measure of survival factor concentration.
  • Transformation of fibroblasts using constitutively expressed src and inducible ras oncogenes.

Main Results:

  • Inhibition of macromolecular synthesis reliably induces apoptosis in fibroblasts.
  • The time to apoptosis onset correlates with endogenous survival factor concentration.
  • Src or ras oncogene transformation decreased survival factor levels, enhancing apoptosis sensitivity.

Conclusions:

  • Fibroblast apoptosis is regulated by a balance between a stable death pathway and labile survival factors.
  • Oncogene-induced transformation reduces endogenous survival factors, sensitizing cells to apoptosis.
  • The timing of apoptosis induction serves as a quantitative measure of survival factor activity.

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