Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2000-10-17
pubmed:abstractText
Increased platinum-DNA adduct removal has been shown by several DNA repair assays to be associated with cisplatin resistance in the A2780/C-series human ovarian cancer model system. In the present study, we provide further evidence that the resistance phenotype of these cell lines is due, in part, to enhanced nucleotide excision repair (NER). Cisplatin resistance was found to be associated with increased UV resistance. Northern blot analysis revealed that increased expression of ERCC1 was also associated with cisplatin resistance in this panel. Several other NER genes were found to be constitutively overexpressed in the most resistant cell line, C200, as compared with the parental A2780 cells. A plasmid substrate containing a site-specific cisplatin adduct was used to measure the nucleotide excision activity of cell extracts prepared from cisplatin-sensitive and -resistant cells. Using this in vitro assay, extracts prepared from C200 cells exhibited approximately 3-fold more activity than extracts prepared from A2780 cells, similar to the difference in UV sensitivity. Complementation of A2780 extracts with ERCC1-XPF protein resulted in approximately 2-fold increased activity, but had little effect on excision in C200 extracts. Overall, these results support a role for the ERCC1-XPF endonuclease as a determinant of increased NER in this cisplatin resistance model.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1305-13
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Increased nucleotide excision repair in cisplatin-resistant ovarian cancer cells: role of ERCC1-XPF.
pubmed:affiliation
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't