title: Dysregulated TGF-beta1-induced Smad signalling occurs as a result of defects in multiple components of the TGF-beta signalling pathway in human head and neck carcinoma cell lines.
abstract: This study examined Smad2- and Smad3-dependent transcription in 12 human head and neck squamous cell carcinoma (HNSCC) cell lines following treatment with transforming growth factor-beta1 (TGF-beta1). A markedly elevated level of TGF-beta1-induced Smad3 signalling was observed in one cell line (H357), whilst four cell lines (BICR31, H314, BICR56, BICR19) demonstrated absence of Smad3-dependent transcription that correlated with loss of TGF-beta1 growth inhibition; TGF-beta1-induced Smad2-dependent transcription was retained in two of these cell lines (H314, BICR31). Using transient expression of TGF-beta signalling components and a Smad3-dependent reporter assay, we show that BICR31 and H314 had defects of Smad4, BICR56 had abnormal TbetaR-II and BICR19 overexpressed Smad7. The results demonstrate that deregulated TGF-beta1-induced Smad signalling is common in HNSCC cell lines and can occur as a result of a variety of defects in the TGF-beta signal transduction pathway.
authors.affiliation: Department of Oral and Dental Science, University of Bristol, Bristol BS1 2LY, UK.
authors.forename: Miranda
authors.initials: M
authors.lastname: Pring
authors.forename: Stephen
authors.initials: S
authors.lastname: Prime
authors.forename: E Kenneth
authors.initials: EK
authors.lastname: Parkinson
authors.forename: Ian
authors.initials: I
authors.lastname: Paterson
mesh_terms: D045744:Cell Line, Tumor; D006258:Head and Neck Neoplasms / Q000503:physiopathology*; D006801:Humans; D010766:Phosphorylation; D010957:Plasmids; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000187:drug effects / Q000502:physiology*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
chemical_list: D051785:Smad Proteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1