c-Myc-induced apoptosis in fibroblasts is inhibited by specific cytokines

EMBO J. 1994 Jul 15;13(14):3286-95.

Abstract

We have investigated the mechanism by which deregulated expression of c-Myc induces death by apoptosis in serum-deprived fibroblasts. We demonstrate that Myc-induced apoptosis in low serum is inhibited by a restricted group of cytokines, principally the insulin-like growth factors and PDGF. Cytokine-mediated protection from apoptosis is not linked to the cytokines' abilities to promote growth. Protection from apoptosis is evident in the post-commitment (mitogen-independent) S/G2/M phases of the cell cycle and also in cells that are profoundly blocked in cell cycle progression by drugs. Moreover, IGF-I inhibition of apoptosis occurs in the absence of protein synthesis, and so does not require immediate early gene expression. We conclude that c-Myc-induced apoptosis does not result from a conflict of growth signals but appears to be a normal physiological aspect of c-Myc function whose execution is regulated by the availability of survival factors. We discuss the possible implications of these findings for models of mammalian cell growth in vivo.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Cells, Cultured
  • Culture Media, Serum-Free
  • Cycloheximide / pharmacology
  • Cytokines / blood
  • Cytokines / pharmacology*
  • Estradiol / pharmacology
  • Etoposide / pharmacology
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Gene Expression Regulation*
  • Gene Expression Regulation, Neoplastic
  • Mesoderm / drug effects
  • Mice
  • Platelet-Derived Growth Factor / pharmacology
  • Protein Biosynthesis
  • Proto-Oncogene Proteins c-myc / genetics*
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Rats
  • Signal Transduction
  • Somatomedins / pharmacology*
  • Thymidine / pharmacology

Substances

  • Culture Media, Serum-Free
  • Cytokines
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-myc
  • Somatomedins
  • Estradiol
  • Etoposide
  • Cycloheximide
  • Thymidine