title: A genomic-scale view of the cAMP response element-enhancer decoy: a tumor target-based genetic tool.
abstract: Enhancer DNA decoy oligodeoxynucleotides (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. Here, we use DNA microarrays to analyze the global effects of the CRE-decoy ODN in cancer cell lines and in tumors grown in nude mice. The CRE-decoy up-regulates the AP-2beta transcription factor gene in tumors but not in the livers of host animals. The up-regulated expression of AP-2beta is clustered with the up-regulation of other genes involved in development and cell differentiation. Concomitantly, another cluster of genes involved in cell proliferation and transformation is down-regulated. The observed alterations indicate that CRE-directed transcription favors tumor growth. The CRE-decoy ODN, therefore, may serve as a target-based genetic tool to treat cancer and other diseases in which CRE-directed transcription is abnormally used.
authors.affiliation: Cellular Biochemistry Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Yee Sook
authors.initials: YS
authors.lastname: Cho
authors.forename: Meyoung-Kon
authors.initials: MK
authors.lastname: Kim
authors.forename: Chris
authors.initials: C
authors.lastname: Cheadle
authors.forename: Catherine
authors.initials: C
authors.lastname: Neary
authors.forename: Yun Gyu
authors.initials: YG
authors.lastname: Park
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Becker
authors.forename: Yoon S
authors.initials: YS
authors.lastname: Cho-Chung
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000235:genetics; D018899:CpG Islands; D000242:Cyclic AMP / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004742:Enhancer Elements, Genetic; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008321:Mammary Glands, Animal; D051379:Mice; D008819:Mice, Nude; D018716:Molecular Mimicry; D009363:Neoplasm Proteins / Q000235:genetics; D009368:Neoplasm Transplantation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D015290:Second Messenger Systems / Q000502:physiology*; D013873:Thionucleotides / Q000737:chemistry / Q000494:pharmacology*; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*; D016042:Transplantation, Heterotopic; D014407:Tumor Cells, Cultured
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009838:Oligodeoxyribonucleotides; C493677:TFAP2B protein, human; C493669:Tfap2b protein, mouse; D013873:Thionucleotides; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D004958:Estradiol; D000242:Cyclic AMP