Source:http://linkedlifedata.com/resource/pubmed/id/15375562
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2004-9-17
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pubmed:abstractText |
Our previous studies revealed a splicing variant (lacking a 42 base pair segment) within the 5'-UTR of the ERCC1 gene, a critical component of the nucleotide excision repair (NER) pathway that plays an important role in the development of chemoresistance in platinum-based anticancer therapy. This 42-bp segment seems to possess a regulatory function in ERCC1 expression and representing the level of clinical response to platinum-treatment in ovarian cancer patients. To confirm the existence of the 42-bp deletion and to investigate the 42-bp function, we performed several experiments and assays. Northern blot analysis and RNase protection assay provide evidence that the 42-bp deletion occurs at RNA level of ERCC1 5'-UTR in both ovarian cancer cell lines and ovarian cancer tissues. Luciferase assay suggests that this gene fragment possesses a regulatory function as an enhancer of ERCC1 gene expression in ovarian cancer cells. In Electrophoretic Mobility Shift Assay (EMSA), a shift band present in the ovarian cancer cell line extracts is consistent with the presence of an intracellular protein that recognizes this specific 42-bp sequence. Further, specific EMSA results with 42-bp probe mutated at the site of RFX-1 indicate different putative-DNA binding proteins, rather than RFX-1. We conclude that the 42-bp sequence within the 5'-UTR influences the expression of ERCC1 and hence can influence response to cisplatin in ovarian cancer therapy.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5' Untranslated Regions,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ERCC1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Endonucleases,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/regulatory factor X transcription...
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1019-6439
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1105-11
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pubmed:dateRevised |
2008-9-5
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pubmed:meshHeading |
pubmed-meshheading:15375562-5' Untranslated Regions,
pubmed-meshheading:15375562-Binding Sites,
pubmed-meshheading:15375562-DNA,
pubmed-meshheading:15375562-DNA-Binding Proteins,
pubmed-meshheading:15375562-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:15375562-Endonucleases,
pubmed-meshheading:15375562-Gene Deletion,
pubmed-meshheading:15375562-Genes, Regulator,
pubmed-meshheading:15375562-Humans,
pubmed-meshheading:15375562-Transcription, Genetic,
pubmed-meshheading:15375562-Transcription Factors
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pubmed:year |
2004
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pubmed:articleTitle |
Confirmation of 42-bp deletion within the ERCC1 5' UTR.
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pubmed:affiliation |
Mary Babb Randolph Cancer Center, Robert C Byrd Health Sciences Center, West Virginia University, Morgantown, WV 26506-9300, USA.
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pubmed:publicationType |
Journal Article
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