| c-Myc induces apoptosis in epithelial cells by both p53-dependent and p53-independent mechanisms. | |
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MedLine Citation:
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PMID: 8570193 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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D Sakamuro; V Eviner; K J Elliott; L Showe; E White; G C Prendergast |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Oncogene Volume: 11 ISSN: 0950-9232 ISO Abbreviation: Oncogene Publication Date: 1995 Dec |
Date Detail:
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Created Date: 1996-03-01 Completed Date: 1996-03-01 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 2411-8 Citation Subset: IM |
Affiliation:
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Wistar Institute, Philadelphia, Pennsylvania 19104, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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CA-10815-28/CA/NCI NIH HHS; CA-53370/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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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