Abstract
In the present study, we show that transforming growth factor beta1 (TGF-beta1) was frequently overexpressed in human head and neck squamous cell carcinomas (HNSCCs) and adjacent tissues in comparison with normal head and neck tissues. To determine the role of TGF-beta1 overexpression in HNSCC carcinogenesis, we generated transgenic mice in which TGF-beta1 transgene expression can be induced in head and neck epithelia. TGF-beta1 transgene induction in head and neck epithelia, at levels similar to those in human HNSCCs, caused severe inflammation and angiogenesis. Consequently, TGF-beta1-transgenic epithelia exhibited hyperproliferation. These phenotypes correlated with enhanced Smad signaling in transgenic epithelia and stroma. Our study suggests that TGF-beta1 overexpression at early stages of HNSCC formation provides a tumor promoting microenvironment.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Carcinoma, Squamous Cell / blood supply
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Carcinoma, Squamous Cell / metabolism*
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Carcinoma, Squamous Cell / pathology
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Cell Division / physiology
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Cell Transformation, Neoplastic / metabolism
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Cell Transformation, Neoplastic / pathology
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Epithelial Cells / metabolism
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Epithelial Cells / pathology
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Head and Neck Neoplasms / blood supply
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Head and Neck Neoplasms / metabolism*
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Head and Neck Neoplasms / pathology
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Humans
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Hyperplasia
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Inflammation / metabolism
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Inflammation / pathology
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Mice
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Mice, Transgenic
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Mouth / metabolism
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Mouth / pathology
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Mouth Mucosa / metabolism
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Mouth Mucosa / pathology
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Neovascularization, Pathologic / metabolism*
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Neovascularization, Pathologic / pathology
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Oropharynx / metabolism
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Oropharynx / pathology
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Transforming Growth Factor beta / biosynthesis*
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta1
Substances
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TGFB1 protein, human
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Tgfb1 protein, mouse
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Transforming Growth Factor beta
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Transforming Growth Factor beta1