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.
MeSH terms
-
Adenocarcinoma / genetics*
-
Adenocarcinoma / pathology
-
Animals
-
Cell Cycle / drug effects
-
Cell Differentiation / genetics
-
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 Profiling / methods*
-
Gene Expression Regulation, Neoplastic / drug effects*
-
Humans
-
Liver / drug effects
-
Liver / metabolism
-
Male
-
Mammary Glands, Animal
-
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*
-
Thionucleotides / chemistry
-
Thionucleotides / pharmacology*
-
Transcription Factor AP-2
-
Transcription Factors / biosynthesis
-
Transcription Factors / genetics
-
Transcription, Genetic / drug effects*
-
Transplantation, Heterotopic
-
Tumor Cells, Cultured
Substances
-
Cyclic AMP Response Element-Binding Protein
-
DNA-Binding Proteins
-
Neoplasm Proteins
-
Oligodeoxyribonucleotides
-
TFAP2B protein, human
-
Tfap2b protein, mouse
-
Thionucleotides
-
Transcription Factor AP-2
-
Transcription Factors
-
Estradiol
-
Cyclic AMP