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[Cancer Research 64, 4405-4410, July 1, 2004]
© 2004 American Association for Cancer Research

Advances in Brief

Overexpression of Transforming Growth Factor ß1 in Head and Neck Epithelia Results in Inflammation, Angiogenesis, and Epithelial Hyperproliferation

Shi-Long Lu1, Douglas Reh1, Allen G. Li1, Jennifer Woods1, Christopher L. Corless2, Molly Kulesz-Martin3,4 and Xiao-Jing Wang1,3,4

Departments of 1 Otolaryngology, 2 Pathology, 3 Dermatology, and 4 Cell and Developmental Biology, Oregon Health & Science University, Portland, Oregon

In the present study, we show that transforming growth factor ß1 (TGF-ß1) 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-ß1 overexpression in HNSCC carcinogenesis, we generated transgenic mice in which TGF-ß1 transgene expression can be induced in head and neck epithelia. TGF-ß1 transgene induction in head and neck epithelia, at levels similar to those in human HNSCCs, caused severe inflammation and angiogenesis. Consequently, TGF-ß1-transgenic epithelia exhibited hyperproliferation. These phenotypes correlated with enhanced Smad signaling in transgenic epithelia and stroma. Our study suggests that TGF-ß1 overexpression at early stages of HNSCC formation provides a tumor promoting microenvironment.




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