Document Detail


c-Myc induces apoptosis in epithelial cells by both p53-dependent and p53-independent mechanisms.
MedLine Citation:
PMID:  8570193     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We tested the hypothesis that wild-type p53 activity is required for c-Myc-dependent apoptosis in epithelial cells. Primary baby rat kidney epithelial cell lines were generated by immortalization through the concerted action of c-Myc and a temperature-sensitive (ts) dominant inhibitory mutant allele of p53 (BRK myc/p53ts cells). When shifted to the permissive temperature for wild-type p53 activity, the BRK myc/p53ts cells underwent growth arrest and apoptosis. However, apoptosis also could be induced by serum deprivation at the nonpermissive temperature, when p53 was in the mutant state. Bcl-2 suppressed both modes of cell death. Apoptosis induced by wild-type p53 but not by serum deprivation was accompanied by G1 cell cycle arrest and increased expression of the Bcl-2 antagonist Bax. We concluded that c-Myc could induce apoptosis in epithelial cells by at least two mechanisms that could be distinguished by their p53 requirement. Our results support the possibility that c-Myc-dependent cell death might be exploited for therapeutic ends during carcinoma development, without regard to p53 status of the target cell.
Authors:
D Sakamuro; V Eviner; K J Elliott; L Showe; E White; G C Prendergast
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Oncogene     Volume:  11     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  1995 Dec 
Date Detail:
Created Date:  1996-03-01     Completed Date:  1996-03-01     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  2411-8     Citation Subset:  IM    
Affiliation:
Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / genetics*
Blood
Cell Line
Epithelium / pathology
Genes, p53*
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins c-bcl-2*
Proto-Oncogene Proteins c-myc / genetics,  physiology*
Rats
Rats, Inbred F344
Temperature
bcl-2-Associated X Protein
Grant Support
ID/Acronym/Agency:
CA-10815-28/CA/NCI NIH HHS; CA-53370/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Bax protein, rat; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Proto-Oncogene Proteins c-myc; 0/bcl-2-Associated X Protein

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