CRE-decoy oligonucleotide-inhibition of gene expression and tumor growth.
Nucleic acid molecules with high affinities for a target transcription factor can be introduced into cells as decoy cis-elements to bind these factors and alter gene expression. This review discusses a synthetic single-stranded palindromic oligonucleotide, which self-hybridizes to form a duplex/hairpin and competes with cAMP response element (CRE) enhancers for binding transcription factors. This oligonucleotide inhibits CRE- and Ap-1-directed gene transcription and promotes growth inhibition in vitro and in vivo in a broad spectrum of cancer cells, without adversely affecting normal cell growth. Evidence presented here suggests that the CRE-decoy oligonucleotide can provide a powerful new means of combating cancers, viral diseases, and other pathological conditions by regulating the expression of cAMP-responsive genes.
Cho-Chung
Y S
YS
Cellular Biochemistry Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, Bethesda, MD 20892-1750, USA.
Park
Y G
YG
Nesterova
M
M
Lee
Y N
YN
Cho
Y S
YS
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos; D006801:Humans; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology* / Q000627:therapeutic use; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D009838:Oligodeoxyribonucleotides; D018808:Transcription Factor AP-1; D016159:Tumor Suppressor Protein p53