A genomic-scale view of the cAMP response element-enhancer decoy: a tumor target-based genetic tool.
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.
Cho
Yee Sook
YS
Cellular Biochemistry Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Kim
Meyoung-Kon
MK
Cheadle
Chris
C
Neary
Catherine
C
Park
Yun Gyu
YG
Becker
Kevin G
KG
Cho-Chung
Yoon S
YS
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
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