Overexpression of transforming growth factor β1 in head and neck epithelia results in inflammation, angiogenesis, and epithelial hyperproliferation

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.