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Targeted inhibition of Stat3 with a decoy oligonucleotide abrogates head and neck cancer cell growth

Academic Article
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Overview

authors

  • Leong, P. L.
  • Andrews, G. A.
  • Johnson, D. E.
  • Dyer, K. F.
  • Xi, S. C.
  • Mai, J. C.
  • Robbins, Paul D.
  • Gadiparthi, S.
  • Burke, N. A.
  • Watkins, S. F.
  • Grandis, J. R.

publication date

  • April 2003

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • The transcription factor signal transducer and activator of transcription 3 (Stat3) is constitutively activated in a variety of cancers including squamous cell carcinoma of the head and neck (SCCHN). Previous investigations have demonstrated that activated Stat3 contributes to a loss of growth control and transformation. To investigate the therapeutic potential of blocking Stat3 in cancer cells, we developed a transcription factor decoy to selectively abrogate activated Stat3. The Stat3 decoy was composed of a 15-mer double-stranded oligonucleotide, which corresponded closely to the Stat3 response element within the c-fos promoter. The Stat3 decoy bound specifically to activated Stat3 and blocked binding of Stat3 to a radiolabeled Stat3 binding element. By contrast, a mutated version of the decoy that differed by only a single base pair did not bind the activated Stat3 protein. Treatment of head and neck cancer cells with the Stat3 decoy inhibited proliferation and Stat3-mediated gene expression, but did not decrease the proliferation of normal oral keratinocytes. Thus, disruption of activated Stat3 by using a transcription factor decoy approach may serve as a novel therapeutic strategy for cancers characterized by constitutive Stat3 activation.

subject areas

  • Apoptosis
  • Carcinoma, Squamous Cell
  • Cell Division
  • DNA-Binding Proteins
  • Head and Neck Neoplasms
  • Humans
  • Luciferases
  • Oligodeoxyribonucleotides, Antisense
  • Proto-Oncogene Proteins c-bcl-2
  • STAT3 Transcription Factor
  • Trans-Activators
  • Tumor Cells, Cultured
  • bcl-X Protein
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Identity

PubMed Central ID

  • PMC153061

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0534764100

PubMed ID

  • 12640143
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Additional Document Info

start page

  • 4138

end page

  • 4143

volume

  • 100

issue

  • 7

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