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
作者： Raymond W M Lung , Kevin A W Lee
关键词: Viral vector 、 ATF1 、 Gene expression 、 Promoter 、 Gene delivery 、 Thymidine kinase 、 Molecular biology 、 Biology 、 Activator (genetics) 、 Fusion gene 、 Cancer research
摘要: 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 potent activator several cAMP-inducible promoters, including the somatostatin promoter. Here we explored potential using promoter to direct toxic gene expression in MMSP cells. When introduced into cells, somatostatin-herpes simplex virus thymidine kinase fusion confers strong cell-specific sensitivity cytotoxic prodrug ganciclovir. Ganciclovir requires ATF-binding site present promoter, indicating that caused by EWS/ATF1. We also tested efficacy recombinant adenoviruses delivery two cell lines (DTC1 Su-ccs-1). Surprisingly, promoters (including somatostatin) are strongly activated EWS/ATF1 transient assays not DTC1 Su-ccs-1 cells when an adenovirus vector. In summary, our findings demonstrate therapy MMSP. However, first-generation vectors cannot be used as vehicles
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