A Genomic-Scale View of the cAMP Response Element-Enhancer Decoy: A Tumor Target-Based Genetic Tool

• Published in: Proceedings of the National Academy of Sciences - PNAS 2002-11, Vol.99 (24), p.15626-15631
• Main Authors: Cho, Yee Sook, Kim, Meyoung-Kon, Cheadle, Chris, Neary, Catherine, Park, Yun Gyu, Becker, Kevin G., Cho-Chung, Yoon S.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - pathology; Animals; Biological Sciences; Cancer; Cell cycle; Cell Cycle - drug effects; Cell Differentiation - genetics; Cell growth; CpG Islands; Cyclic AMP - physiology; Cyclic AMP Response Element-Binding Protein - antagonists & inhibitors; Cyclic AMP Response Element-Binding Protein - metabolism; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Enhancer Elements, Genetic; Estradiol - pharmacology; Female; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic - drug effects; Genes; Genomics; Humans; Liver; Liver - drug effects; Liver - metabolism; Male; Mammary Glands, Animal; Medical research; Mice; Mice, Nude; Molecular Mimicry; Neoplasm Proteins - genetics; Neoplasm Transplantation; Oligodeoxyribonucleotides - chemistry; Oligodeoxyribonucleotides - pharmacology; Oligonucleotide Array Sequence Analysis; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Second Messenger Systems - physiology; Signatures; Thionucleotides - chemistry; Thionucleotides - pharmacology; Transcription Factor AP-2; Transcription factors; Transcription Factors - biosynthesis; Transcription Factors - genetics; Transcription, Genetic - drug effects; Transplantation, Heterotopic; Tumor Cells, Cultured; Tumors; Up regulation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.242617799

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-2β transcription factor gene in tumors but not in the livers of host animals. The up-regulated expression of AP-2β 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.