Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1998-1-8
pubmed:abstractText
Thymidylate synthase (TS) expression has been characterized for a panel of eight human colorectal carcinoma and five human leukaemia cell lines, to relate differences in intrinsic TS activity, protein and mRNA levels to growth inhibition caused by continuous exposure to THYMITAQ, a specific non-classical antifolate TS inhibitor. Although a 20-fold variation in sensitivity to THYMITAQ was found within the colorectal cell line panel (IC50 0.12-2.7 microM), sensitivity was not related to TS activity, TS protein or TS mRNA levels. For the leukaemic cell lines, only a twofold range in sensitivity to THYMITAQ was observed (IC50 0.87-2.3 microM), and this did not correlate with TS activity, TS protein or TS mRNA levels. Across all of the cell lines, TS activity was linearly related to TS protein levels (r2 = 0.87, P < 0.0001). However, for both the colorectal and leukaemia cell line panels, no relationship was found between TS mRNA/18S rRNA ratios and either TS activity or TS protein, consistent with the importance of post-transcriptional mechanisms in regulating TS activity. Two of the colorectal cell lines (BE and HCT116) and one of the human leukaemic cell lines (HL60), were intrinsically resistant to THYMITAQ (IC50 > 2 microM) in the absence of TS overexpression, suggesting that, subsequent to TS inhibition, events such as DNA repair and tolerance to apoptotic stimuli are also important determinants of sensitivity to THYMITAQ.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-1355260, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-1438236, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-1737372, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-1827310, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-1913676, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-1924359, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-2253202, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-2415245, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-2440339, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-2971871, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-2971872, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-3049954, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-6144683, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-6312838, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-7389797, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-7508170, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-7537518, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-7537519, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-7683570, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-7763285, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-7882343, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-7989939, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-8324744, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-8328986, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-8459400, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-8612303, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-8624289, http://linkedlifedata.com/resource/pubmed/commentcorrection/9413945-9816165
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0007-0920
pubmed:author
pubmed:issnType
Print
pubmed:volume
76
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1579-85
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
The relationship between intrinsic thymidylate synthase expression and sensitivity to THYMITAQ in human leukaemia and colorectal carcinoma cell lines.
pubmed:affiliation
Department of Paediatric Oncology, Sir James Spence Institute of Child Health, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't