Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2000-11-3
pubmed:abstractText
Previously, we showed that expression of nm23-H1 is associated inversely with sensitivity to cisplatin in human oesophageal squamous cell carcinoma (OSCC). The present study was undertaken to investigate the association of nm23-H1 expression with cisplatin-induced DNA damage in OSCC using antisense nm23-H1 transfectants. YES-2/AS-12, an antisense nm23-H1-transfected OSCC cell line, showed significantly reduced expression of intracellular nm23-H1 protein compared with that in parental YES-2 cells and YES-2/Neo transfectants. Surface expression of nm23-H1 protein was not observed in any of the three cell lines. PCR analysis for DNA damage demonstrated that YES-2/AS-12 cells were more resistant to nuclear and mitochondrial DNA damage by cisplatin than were YES-2/Neo cells. In addition, mitochondrial membrane potentials and DNA fragmentation assays confirmed that YES-2/AS-12 was more resistant than YES-2/Neo to apoptosis induced by cisplatin. In contrast, YES-2/AS-12 was more sensitive to ouabain, a selective inhibitor of Na(+), K(+)-ATPase, than YES-2 and YES-2/Neo. Pre-treatment with ouabain resulted in no differences in cisplatin sensitivity between the three cell lines examined. Intracellular platinum level in YES-2/AS-12 was significantly lower than that in YES-2 and YES-2/Neo following incubation with cisplatin, whereas ouabain pre-treatment resulted in no differences in intracellular platinum accumulations between the three cell lines. Our data support the conclusion that reduced expression of intracellular nm23-H1 in OSCC cells is associated with cisplatin resistance via the prevention of both nuclear and mitochondrial DNA damage and suggest that it may be related to Na(+), K(+)-ATPase activity, which is responsible for intracellular cisplatin accumulation.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-10050884, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-10082974, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-10200955, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-10232605, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-10378785, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-10424745, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-10487609, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-10507772, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-10604725, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-10680588, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-1321145, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-1325827, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-1630919, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-1648442, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-1685630, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-1713575, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-1988104, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-2448875, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-3346912, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-7530600, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-7670138, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-7753115, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-8102131, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-8150528, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-8242627, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-8386830, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-8395676, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-8633923, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-8636741, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-8674043, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-8826870, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-8912537, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-8974001, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-9095172, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-9216861, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-9219551, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-9219702, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-9242435, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-9558479, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-9593706, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-9743288, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-9831363, http://linkedlifedata.com/resource/pubmed/commentcorrection/11027435-9886926
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Cisplatin, http://linkedlifedata.com/resource/pubmed/chemical/DNA, http://linkedlifedata.com/resource/pubmed/chemical/DNA, Antisense, http://linkedlifedata.com/resource/pubmed/chemical/DNA, Mitochondrial, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Monomeric GTP-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/NM23 Nucleoside Diphosphate Kinases, http://linkedlifedata.com/resource/pubmed/chemical/NME1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Nucleoside-Diphosphate Kinase, http://linkedlifedata.com/resource/pubmed/chemical/Ouabain, http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Potassium-Exchanging ATPase, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0007-0920
pubmed:author
pubmed:copyrightInfo
Copyright 2000 Cancer Research Campaign.
pubmed:issnType
Print
pubmed:volume
83
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1209-15
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
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