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pubmed-article:9566690pubmed:abstractTextTumor necrosis factor-alpha (TNF-alpha) is a macrophage-derived multifunctional cytokine that acts as a cytostatic or cytotoxic agent in many tumor cells. However, the molecular mechanisms by which tumor cells become sensitive to the cytotoxic action of TNF-alpha are not clear. In this study we demonstrated that the cytotoxicity of TNF-alpha markedly increased in c-Myc overexpressing tumor cells. The stomach cancer cell line, SNU-16, in which c-Myc expression is high due to gene amplification, showed programmed cell death detected by DNA fragmentation and morphological changes. An antisense c-myc S-oligonucleotide specifically inhibited the TNF-alpha-induced apoptosis of SNU-16 cells, provided that the oligonucleotide was added 4 h prior to TNF-alpha treatment. Western immunoblot analysis of p53 and Bax showed that in this cell line, TNF-alpha increased the level of these proteins in a time-dependent manner and that this effect lasted for 12 h. Taken together these data indicate that the deregulation of c-Myc plays an important role in sensitizing tumor cells to TNF-alpha. Furthermore, TNF-alpha-induced apoptosis in the SNU-16 cell line showed increased expression of p53 and Bax protein levels following TNF-alpha treatment. Therefore, we suggest that TNF-alpha-induced apoptosis, which is cytotoxic to tumor cells, is coupled with a p53 and Bax apoptotic pathway.lld:pubmed
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pubmed-article:9566690pubmed:authorpubmed-author:LeeS HSHlld:pubmed
pubmed-article:9566690pubmed:authorpubmed-author:HongS ISIlld:pubmed
pubmed-article:9566690pubmed:authorpubmed-author:ParkM JMJlld:pubmed
pubmed-article:9566690pubmed:authorpubmed-author:JangJ JJJlld:pubmed
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pubmed-article:9566690pubmed:pagination17-23lld:pubmed
pubmed-article:9566690pubmed:dateRevised2006-11-15lld:pubmed
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pubmed-article:9566690pubmed:articleTitleIncreased susceptibility of the c-Myc overexpressing cell line, SNU-16, to TNF-alpha.lld:pubmed
pubmed-article:9566690pubmed:affiliationLaboratory of Cell Biology, Korea Cancer Center Hospital, Seoul, South Korea.lld:pubmed
pubmed-article:9566690pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:9566690pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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