Related Experiment Videos
A genomic-scale view of the cAMP response element-enhancer decoy: a tumor target-based genetic tool
Yee Sook Cho1, Meyoung-Kon Kim, Chris Cheadle
1Cellular Biochemistry Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
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.
Insights
A novel cancer therapy uses a cAMP response element (CRE) decoy oligodeoxynucleotide (ODN) to block tumor growth by inhibiting CRE-directed gene transcription. This targeted approach shows promise for treating cancers and other diseases.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- Enhancer DNA decoy oligodeoxynucleotides (ODNs) function by competing with transcription factors.
- A specific decoy ODN targeting the cAMP response element (CRE) inhibits CRE-directed gene transcription.
- This CRE-decoy ODN has demonstrated the ability to inhibit tumor growth without impacting normal cell proliferation.
Purpose of the Study:
- To investigate the global gene expression effects of the CRE-decoy ODN in cancer cell lines and in vivo tumor models.
- To understand the molecular mechanisms by which the CRE-decoy ODN influences tumor biology.
- To evaluate the potential of CRE-decoy ODN as a targeted therapeutic agent for cancer.
Main Methods:
- Utilized DNA microarrays to perform a comprehensive analysis of gene expression profiles.
- Examined the effects of CRE-decoy ODN treatment in both cancer cell lines and xenograft tumor models in nude mice.
- Analyzed gene expression changes in tumor tissues and host animal livers.
Main Results:
- The CRE-decoy ODN treatment led to the up-regulation of the AP-2beta transcription factor gene specifically within tumors.
- Observed a coordinated up-regulation of genes associated with development and cell differentiation in tumors.
- Concurrently, a down-regulation of genes involved in cell proliferation and transformation was detected in the tumors.
- Gene expression changes in host animal livers were distinct from those observed in tumors.
Conclusions:
- CRE-directed transcription plays a significant role in promoting tumor growth.
- The CRE-decoy ODN effectively modulates gene expression pathways critical for cancer progression.
- This targeted genetic tool holds potential for the treatment of cancers and other diseases characterized by aberrant CRE-directed transcription.