CRE-enhancer DNA decoy: a tumor target-based genetic tool.
Enhancer DNA decoy oligonucleotides (ODNs) inhibit transcription by competing for transcription factors. A decoy ODN composed of the cAMP response element (CRE) inhibits CRE-directed gene transcription and tumor growth without affecting normal cell growth. We used DNA microarrays to analyze the global gene expression in tumors exposed to the CRE-decoy ODN. The CRE decoy upregulated the AP-2beta transcription factor gene in tumors but not in the livers of host animals. The upregulated expression of AP-2beta was clustered with other upregulated genes involved in development and cell differentiation. Concomitantly, another cluster of genes involved in cell proliferation and transformation was downregulated. The observed alterations indicate that CRE-directed transcription favors tumor growth. Evidence presented here suggests that the CRE-decoy ODN may provide a target-based genetic tool for treating cancer, viral diseases, and other diseases in which CRE-directed transcription is abnormally used.
Cho-Chung
Yoon S
YS
Cellular Biochemistry Section, Basic Research Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1750, USA. yc12b@nih.gov
D000818:Animals; D020869:Gene Expression Profiling; D008099:Liver / Q000187:drug effects; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000494:pharmacology*; D020218:Response Elements / Q000187:drug effects* / Q000235:genetics
D009838:Oligodeoxyribonucleotides