NDLI: Constitutive activation of Stat3 signaling abrogates apoptosis in squamous cell carcinogenesis in vivo.

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Constitutive activation of Stat3 signaling abrogates apoptosis in squamous cell carcinogenesis in vivo.

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Constitutive activation of Stat3 signaling abrogates apoptosis in squamous cell carcinogenesis in vivo.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Grandis, J. R. Endo, S. Zeng, Q. Watkins, S. C. He, Y. Melhem, M. F. Kim, J. D. Huang, L. Drenning, S. D. Johnson, D. E.
Description	Author Affiliation: Grandis JR ( Department of Otolaryngology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA. jgrandis+@pitt.edu);
Abstract	Field cancerization predisposes the upper aerodigestive tract mucosa to the formation of multiple primary tumors, when exposed to environmental carcinogens. Up-regulation of epidermal growth factor receptor occurs early in squamous cell carcinogenesis and is critical for the loss of growth control in a variety of human cancers, including head and neck squamous cell carcinomas. In these tumor cells in culture, epidermal growth factor receptor stimulation initiates signaling via persistent activation of selective STAT proteins. To determine the timing of Stat3 activation in head and neck carcinogenesis, we studied the expression and constitutive activation of Stat3 in tumors and normal mucosa from patients with head and neck cancer compared with mucosa from controls without cancer. Stat3 was up-regulated and constitutively activated in both primary human head and neck tumors as well as in normal mucosa from these cancer patients compared with control normal mucosa from patients without cancer. In vivo liposome-mediated gene therapy with a Stat3 antisense plasmid efficiently inhibited Stat3 activation, increased tumor cell apoptosis, and decreased Bcl-x(L) expression in a head and neck xenograft model. These findings provide evidence that constitutively activated Stat3 is an early event in head and neck carcinogenesis that contributes to the loss of growth control by an anti-apoptotic mechanism.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	8
Volume Number	97
Language	English
Publisher	National Academy of Sciences
Publisher Date	2000-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Apoptosis Carcinoma, Squamous Cell Pathology DNA-Binding Proteins Metabolism Head And Neck Neoplasms Signal Transduction Trans-Activators Animals Genetics Therapy Genetic Therapy Liposomes Mice Mice, Nude Neoplasm Transplantation Oligonucleotides, Antisense Pharmacology Receptor, Epidermal Growth Factor STAT3 Transcription Factor Transforming Growth Factors Tumor Cells, Cultured Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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