Source:http://linkedlifedata.com/resource/pubmed/id/10766345
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2000-8-4
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pubmed:abstractText |
The cellular oncoprotein Ewing's sarcoma oncogene (EWS)/activating transcription factor 1 (ATF1) is a highly specific marker for malignant melanoma of soft parts (MMSP) and is a potent activator of several cAMP-inducible promoters, including the somatostatin promoter. Here we explored the potential for using the somatostatin promoter to direct toxic gene expression in MMSP cells. When introduced into MMSP cells, a somatostatin-herpes simplex virus thymidine kinase fusion gene confers strong and cell-specific sensitivity to the cytotoxic prodrug ganciclovir. Ganciclovir sensitivity requires the ATF-binding site present in the somatostatin promoter, indicating that toxic gene expression is caused by EWS/ATF1. We also tested the efficacy of recombinant adenoviruses adenoviruses for gene delivery and expression in two MMSP cell lines (DTC1 and Su-ccs-1). Surprisingly, several promoters (including somatostatin) that are strongly activated by EWS/ATF1 in transient assays are not activated in DTC1 and Su-ccs-1 cells when present in an adenovirus vector. In summary, our findings demonstrate the potential for using the somatostatin promoter for cytotoxic prodrug therapy for MMSP. However, first-generation adenovirus vectors cannot be used as promoter delivery vehicles for toxic gene expression in MMSP cells.
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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/EWS-ATF1 fusion protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins, Fusion,
http://linkedlifedata.com/resource/pubmed/chemical/Prodrugs,
http://linkedlifedata.com/resource/pubmed/chemical/Somatostatin,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0929-1903
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
7
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
396-406
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10766345-Adenoviridae,
pubmed-meshheading:10766345-Animals,
pubmed-meshheading:10766345-Gene Expression Regulation, Viral,
pubmed-meshheading:10766345-Genetic Vectors,
pubmed-meshheading:10766345-Humans,
pubmed-meshheading:10766345-Oncogene Proteins, Fusion,
pubmed-meshheading:10766345-PC12 Cells,
pubmed-meshheading:10766345-Prodrugs,
pubmed-meshheading:10766345-Promoter Regions, Genetic,
pubmed-meshheading:10766345-Rats,
pubmed-meshheading:10766345-Recombination, Genetic,
pubmed-meshheading:10766345-Sarcoma, Clear Cell,
pubmed-meshheading:10766345-Somatostatin,
pubmed-meshheading:10766345-Transcription Factors,
pubmed-meshheading:10766345-Tumor Cells, Cultured,
pubmed-meshheading:10766345-Virus Replication
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pubmed:year |
2000
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pubmed:articleTitle |
The cellular oncogene EWS/activating transcription factor 1 is unable to activate adenovirus-borne promoters: implications for cytotoxic prodrug therapy of malignant melanoma of soft parts.
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pubmed:affiliation |
Department of Biology, Hong Kong University of Science and Technology, Kowloon, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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