Targeted inhibition of Stat3 with a decoy oligonucleotide abrogates head and neck cancer cell growth
-
- Paul L. Leong
- Departments of Otolaryngology, Medicine, Pharmacology, Molecular Genetics and Biochemistry, and Cell Biology and Physiology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15260
-
- Genevieve A. Andrews
- Departments of Otolaryngology, Medicine, Pharmacology, Molecular Genetics and Biochemistry, and Cell Biology and Physiology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15260
-
- Daniel E. Johnson
- Departments of Otolaryngology, Medicine, Pharmacology, Molecular Genetics and Biochemistry, and Cell Biology and Physiology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15260
-
- Kevin F. Dyer
- Departments of Otolaryngology, Medicine, Pharmacology, Molecular Genetics and Biochemistry, and Cell Biology and Physiology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15260
-
- Sichuan Xi
- Departments of Otolaryngology, Medicine, Pharmacology, Molecular Genetics and Biochemistry, and Cell Biology and Physiology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15260
-
- Jeffrey C. Mai
- Departments of Otolaryngology, Medicine, Pharmacology, Molecular Genetics and Biochemistry, and Cell Biology and Physiology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15260
-
- Paul D. Robbins
- Departments of Otolaryngology, Medicine, Pharmacology, Molecular Genetics and Biochemistry, and Cell Biology and Physiology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15260
-
- Seshu Gadiparthi
- Departments of Otolaryngology, Medicine, Pharmacology, Molecular Genetics and Biochemistry, and Cell Biology and Physiology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15260
-
- Nancy A. Burke
- Departments of Otolaryngology, Medicine, Pharmacology, Molecular Genetics and Biochemistry, and Cell Biology and Physiology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15260
-
- Simon F. Watkins
- Departments of Otolaryngology, Medicine, Pharmacology, Molecular Genetics and Biochemistry, and Cell Biology and Physiology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15260
-
- Jennifer Rubin Grandis
- Departments of Otolaryngology, Medicine, Pharmacology, Molecular Genetics and Biochemistry, and Cell Biology and Physiology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15260
Description
<jats:p> The transcription factor <jats:underline>s</jats:underline> ignal <jats:underline>t</jats:underline> ransducer and <jats:underline>a</jats:underline> ctivator of <jats:underline>t</jats:underline> ranscription 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. </jats:p>
Journal
-
- Proceedings of the National Academy of Sciences
-
Proceedings of the National Academy of Sciences 100 (7), 4138-4143, 2003-03-14
Proceedings of the National Academy of Sciences
- Tweet
Details 詳細情報について
-
- CRID
- 1360292619104903424
-
- ISSN
- 10916490
- 00278424
-
- Data Source
-
- Crossref