Signal transduction in the human thyrocyte and its perversion in thyroid tumors

The study of normal signal transduction pathways regulating the proliferation and differentiation of a cell type allows to predict and to understand the perversions of these pathways which lead to tumorigenesis. In the case of the human thyroid cell, three cascades are mostly involved in tumorigenesis: The TSH receptor-cyclic AMP cascade, the constitutive activation of which leads to autonomous adenomas and congenital hyperthyroidism. The growth factor-Ras-MAP kinase pathway, whose constitutive activation causes follicular and papillary carcinomas. The PI-3Kinase-PKB pathway, the activity of which is necessary for both pathways and the corresponding tumors. The pathways and genetic events affecting them are described. Caveats in the use of models and the interpretation of results are formulated and the still pending questions are outlined. (C) 2009 Elsevier Ireland Ltd. All rights reserved.