Our group has pioneered the study of thyroid cell proliferation and differentiation and has demonstrated in these cells the
existence of three cascades of mitogenic signal transduction, TSH/adenylyl cyclase/cAMP, EGF-HGF/ras/MAPK and phorbol
esters/phospholipase C/protein kinase C. The cAMP pathway promotes both proliferation and differentiation within thyrocytes and is causatively
involved in goitrogenesis, tumor promotion and generation of hyperfunctional adenomas. The positive regulation of thyroid cell cycle by
cAMP is unique as it targets the assembly and activation of complexes of pre-existing cyclin D and CDK4 without involving most of
the intermediaries of known mitogenic signaling cascades. Ongoing studies include the identification by molecular biology
techniques (PCR-derived methods, microarrays) of new genes regulated by cAMP and the investigation by proteomic approaches and
two-hybrids methology of the novel mechanisms of CDK4 activation by cAMP. Extension of this work to thyroid tumors involves the analysis of
gene expression profiles in those tissues by the microarray technology.