环磷酸腺苷反应元件增强子诱饵的基因组规模视图：一种基于肿瘤靶点的基因工具。
A genomic-scale view of the cAMP response element-enhancer decoy: a tumor target-based genetic tool.
作者信息
Cho Yee Sook, Kim Meyoung-Kon, Cheadle Chris, Neary Catherine, Park Yun Gyu, Becker Kevin G, Cho-Chung Yoon S
机构信息
Cellular Biochemistry Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15626-31. doi: 10.1073/pnas.242617799. Epub 2002 Nov 18.
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.
增强子DNA诱饵寡脱氧核苷酸（ODN）通过竞争转录因子来抑制转录。一种由环磷酸腺苷反应元件（CRE）组成的诱饵ODN可抑制CRE指导的基因转录和肿瘤生长，而不影响正常细胞生长。在此，我们使用DNA微阵列分析CRE诱饵ODN对癌细胞系和裸鼠体内生长肿瘤的整体影响。CRE诱饵在肿瘤中上调AP-2β转录因子基因，但在宿主动物的肝脏中则不然。AP-2β的上调表达与其他参与发育和细胞分化的基因上调聚集在一起。同时，另一组参与细胞增殖和转化的基因被下调。观察到的变化表明，CRE指导的转录有利于肿瘤生长。因此，CRE诱饵ODN可作为一种基于靶点的基因工具，用于治疗癌症和其他异常使用CRE指导转录的疾病。
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