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pubmed-article:10766345pubmed:abstractTextThe 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.lld:pubmed
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pubmed-article:10766345pubmed:authorpubmed-author:LuntR RRRlld:pubmed
pubmed-article:10766345pubmed:authorpubmed-author:MenJ LJLlld:pubmed
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pubmed-article:10766345pubmed:volume7lld:pubmed
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pubmed-article:10766345pubmed:pagination396-406lld:pubmed
pubmed-article:10766345pubmed:dateRevised2008-11-21lld:pubmed
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pubmed-article:10766345pubmed:year2000lld:pubmed
pubmed-article:10766345pubmed:articleTitleThe 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.lld:pubmed
pubmed-article:10766345pubmed:affiliationDepartment of Biology, Hong Kong University of Science and Technology, Kowloon, China.lld:pubmed
pubmed-article:10766345pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:10766345pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed