Dual blockade of cyclic AMP response element- (CRE) and AP-1-directed transcription by CRE-transcription factor decoy oligonucleotide: Gene- specific inhibition of tumor growth

Yun Gyu Park, Maria Nesterova, Sudhir Agrawal, Yoon S. Cho-Chung

    Research output: Contribution to journalArticlepeer-review

    119 Citations (Scopus)

    Abstract

    Alteration of gene transcription by inhibition of specific transcriptional regulatory proteins has important therapeutic potential. Synthetic double-stranded phosphorothioate oligonucleotides with high affinity for a target transcription factor can be introduced into cells as decoy cis-elements to bind the factors and alter gene expression. The CRE (cyclic AMP response element)transcription factor complex is a pleiotropic activator that participates in the induction of a wide variety of cellular and viral genes. Because the CRE cis-element, TGACGTCA, is palindromic, a synthetic single-stranded oligonucleotide composed of the CRE sequence self- hybridizes to form a duplex/hairpin. Herein we report that the CRE- palindromic oligonucleotide can penetrate into cells, compete with CRE enhancers for binding transcription factors, and specifically interfere with CRE- and AP-1-directed transcription in vivo. These oligonucleotides restrained tumor cell proliferation, without affecting the growth of noncancerous cells. This decoy oligonucleotide approach offers great promise as a tool for defining cellular regulatory processes and treating cancer and other diseases.

    Original languageEnglish
    Pages (from-to)1573-1580
    Number of pages8
    JournalJournal of Biological Chemistry
    Volume274
    Issue number3
    DOIs
    Publication statusPublished - 1999 Jan 15

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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