Linked Life Data

9414664

Source:http://linkedlifedata.com/resource/pubmed/id/9414664

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1998-1-15
pubmed:abstractText
Inactivation of p16INK4, an inhibitor of cyclin-dependent kinases 4 (CDK4) and 6 (CDK6), may be essential for oncogenesis in non-small cell lung cancer (NSCLC). We examined the sensitivity of two clones of p16INK4-transfected NSCLC cell line with homozygous deletion of p16INK4, A549/p16-1 and 2, to DNA topoisomerase I (topo I) inhibitors. A549/p16-1 and -2 showed 7.7- and 9.1-fold increases in sensitivity to CPT-11 (11,7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin ), respectively, compared with A549 cells. Ectopic p16INK4-expressing cells also showed approximately 4.0-fold increase in sensitivity to SN-38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of CPT-11, compared to the parent cells. The topo I-mediated DNA relaxation activities of ectopic p16INK4-expressing cells were approximately 5 times higher than those of the parent cells. Northern and western blot analyses indicate that these increased topo I activities of ectopic p16INK4-expressing cells were due to an elevated topo I mRNA level and an increase in topo I protein. The chemosensitivity to topo I inhibitors, topo I mRNA level, protein content and activity of a p16INK4 revertant, lacking functional p16INK4, tended to be restored toward those of the parental phenotype to some extent. These results suggest that p16INK4 expression is closely associated with the increased sensitivity of ectopic p16INK4-expressing NSCLC cells to topo I inhibitors. The up-regulation of topo I mRNA level, protein content and activity may be responsible for this hypersensitivity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0910-5050
pubmed:author
pubmed:issnType
Print
pubmed:volume
88
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1009-16
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
p16INK4 expression is associated with the increased sensitivity of human non-small cell lung cancer cells to DNA topoisomerase I inhibitors.
pubmed:affiliation
Pharmacology Division, National Cancer Center Research Institute, Tokyo.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't