Document Detail


c-Myc-induced apoptosis in fibroblasts is inhibited by specific cytokines.
MedLine Citation:
PMID:  8045259     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
E A Harrington; M R Bennett; A Fanidi; G I Evan
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  The EMBO journal     Volume:  13     ISSN:  0261-4189     ISO Abbreviation:  EMBO J.     Publication Date:  1994 Jul 
Date Detail:
Created Date:  1994-09-01     Completed Date:  1994-09-01     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  3286-95     Citation Subset:  IM    
Affiliation:
Biochemistry of the Cell Nucleus Laboratory, Imperial Cancer Research Fund Laboratories, London, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects,  physiology*
Cells, Cultured
Culture Media, Serum-Free
Cycloheximide / pharmacology
Cytokines / blood,  pharmacology*
Estradiol / pharmacology
Etoposide / pharmacology
Fibroblasts / cytology,  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*,  metabolism*
Rats
Signal Transduction
Somatomedins / pharmacology*
Thymidine / pharmacology
Chemical
Reg. No./Substance:
0/Culture Media, Serum-Free; 0/Cytokines; 0/Platelet-Derived Growth Factor; 0/Proto-Oncogene Proteins c-myc; 0/Somatomedins; 33419-42-0/Etoposide; 50-28-2/Estradiol; 50-89-5/Thymidine; 66-81-9/Cycloheximide
Comments/Corrections

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