Overexpression of Transforming Growth Factor β1 in Head and Neck Epithelia Results in Inflammation, Angiogenesis, and Epithelial Hyperproliferation

Abstract

In the present study, we show that transforming growth factor β1 (TGF-β1) 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-β1 overexpression in HNSCC carcinogenesis, we generated transgenic mice in which TGF-β1 transgene expression can be induced in head and neck epithelia. TGF-β1 transgene induction in head and neck epithelia, at levels similar to those in human HNSCCs, caused severe inflammation and angiogenesis. Consequently, TGF-β1-transgenic epithelia exhibited hyperproliferation. These phenotypes correlated with enhanced Smad signaling in transgenic epithelia and stroma. Our study suggests that TGF-β1 overexpression at early stages of HNSCC formation provides a tumor promoting microenvironment.