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CRE-enhancer DNA decoy: a tumor target-based genetic tool
1Cellular Biochemistry Section, Basic Research Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1750, USA. yc12b@nih.gov
Annals of the New York Academy of Sciences
|January 31, 2004
Summary
A cAMP response element (CRE) decoy oligonucleotide inhibits tumor growth by altering gene expression. This targeted genetic tool shows potential for treating cancers and other diseases driven by CRE-directed transcription.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- Enhancer DNA decoy oligonucleotides (ODNs) modulate gene transcription by sequestering transcription factors.
- The cAMP response element (CRE) decoy ODN specifically targets CRE-mediated transcription.
- CRE-directed transcription plays a role in tumor growth and development.
Purpose of the Study:
- To investigate the global gene expression changes in tumors treated with a CRE decoy ODN.
- To determine the therapeutic potential of CRE decoy ODNs in cancer treatment.
- To elucidate the molecular mechanisms by which CRE decoy ODNs affect tumor biology.
Main Methods:
- DNA microarray analysis was employed to assess global gene expression profiles.
- Tumor tissues and host animal livers were analyzed post-CRE decoy ODN treatment.
- Bioinformatic analysis was used to identify upregulated and downregulated gene clusters.
Main Results:
- The CRE decoy ODN significantly upregulated the AP-2beta transcription factor gene specifically in tumors.
- Upregulated genes in treated tumors were associated with development and cell differentiation.
- Genes involved in cell proliferation and transformation were concurrently downregulated in tumors.
Conclusions:
- CRE-directed transcription actively promotes tumor growth.
- The CRE decoy ODN effectively alters tumor gene expression, inhibiting proliferation and promoting differentiation.
- CRE decoy ODNs represent a promising targeted genetic therapy for cancers and other diseases involving aberrant CRE activity.