Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1994-9-19
pubmed:abstractText
The phosphoprotein c-Myc has the potential to kill cells by apoptosis. To investigate whether c-Myc is involved in tumor necrosis factor alpha (TNF-alpha)-mediated cell killing, we have examined two HeLa cell lines (D98 and H21) which show dramatic differences in their susceptibilities to TNF-alpha cytotoxicity. Northern (RNA) blot analyses showed that there were no significant differences between these cell lines in basal or TNF-alpha-induced mRNA expression for a variety of proteins, including manganous superoxide dismutase, A20 zinc finger protein, plasminogen activator inhibitor type 2, and hsp70, all of which are known to influence the susceptibility of certain cells to TNF-alpha killing. On the other hand, there was a dramatic increase in c-Myc mRNA expression in TNF-alpha-sensitive D98 cells, but not in TNF-alpha-resistant H21 cells, which was only observed when the cells were treated with cycloheximide. Western blot (immunoblot) analyses revealed that even in the absence of TNF-alpha or cycloheximide, c-Myc was detectable only in nuclear extracts of TNF-alpha-sensitive D98 cells, implying a role for preexisting c-Myc in TNF-alpha killing. In support of this interpretation, a c-myc antisense oligonucleotide specifically inhibited the TNF-alpha killing of D98 cells, provided that the oligonucleotide was added 6 h prior to TNF-alpha treatment. Either dexamethasone treatment or transient expression of c-myc antisense cDNA fragments decreased nuclear c-Myc in D98 cells and rendered the cells more resistant to TNF-alpha cytotoxicity. Nuclear c-Myc was also detectable in a TNF-alpha-sensitive human HT-1080 fibrosarcoma cell line, but it was undetectable in a derivative of HT-1080 (SS-HT-1080) known to be resistant to TNF-alpha killing because of overexpression of plasminogen activator inhibitor type 2. HT-1080 cells transfected with antisense c-myc cDNA had significantly less nuclear c-Myc and were resistant to TNF-alpha cytotoxicity. Together, these data indicate that a nuclear transcription factor, c-Myc, plays an important role in sensitizing two different tumor cell types to TNF-alpha cytotoxicity.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-1317006, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-1372394, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-1378649, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-1396553, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-1406975, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-1406976, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-1555236, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-1618749, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-1649771, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-1665907, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-1713127, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-1852210, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-1923514, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-1939146, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-2006410, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-2172061, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-2174582, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-2182946, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-2269425, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-2415519, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-2426570, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-2434436, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-2441999, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-2476237, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-2531778, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-2659598, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-2771659, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-2925656, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-2944600, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-2960901, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-2967329, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-2994048, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-2999773, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-3040777, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-3097823, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-3171180, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-3277717, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-3377783, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-3416298, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-3496595, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-3933111, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-518835, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-5432063, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-6203430, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-6288259, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-6930649, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-7684376, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-7902825, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-8170983, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-8266081, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-8278410, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-8344250, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-8397073, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-8425218, http://linkedlifedata.com/resource/pubmed/commentcorrection/8065303-8453273
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0270-7306
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:geneSymbol
c-myc
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5661-70
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
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