Abstract
Transforming growth factor-β (TGF-β) is a multifunctional cytokine. In the present study we have investigated the expression of TGF-β receptors (TβR’s) and SMAD proteins in non-neoplastic and neoplastic thyroid follicle cells. We found expression of all TβR’s (type I, II and III) and SMAD proteins analysed (Smad2, Smad3, Smad4, Smad6 and Smad7). Five out of six human anaplastic thyroid carcinoma cell lines were growth inhibited by addition of TGF-β1, and therefore considered to be TGF-responsive. One cell line however, HTh 7, did not respond to TGF-β1 with growth inhibition, induction of the extracellular matrix protein fibronectin or immediate early genes junB , Smad6 and Smad7 mRNA. Analysis of the TGF-β intracellular signalling pathway in HTh 7 cells showed that receptors were capable of signalling, e.g. Smad2 phosphorylation and SMAD nuclear translocation. In summary, our data shows abundant expression of TGF-β signalling components in thyroid follicle cells, and the escape from TGF-β sensitivity in one anaplastic thyroid carcinoma despite an apparently functional TGF-β/SMAD-signalling pathway, indicating a novel mechanism for TGF-β insensitivity.
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