Overexpression of transforming growth factor beta1 in head and neck epithelia results in inflammation, angiogenesis, and epithelial hyperproliferation.
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.
Lu
Shi-Long
SL
Department of Otolaryngology, Oregon Health & Science University, Portland, USA.
Reh
Douglas
D
Li
Allen G
AG
Woods
Jennifer
J
Corless
Christopher L
CL
Kulesz-Martin
Molly
M
Wang
Xiao-Jing
XJ
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009055:Mouth / Q000378:metabolism / Q000473:pathology; D009061:Mouth Mucosa / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D009960:Oropharynx / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D053773:Transforming Growth Factor beta1
C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1