Control of cell proliferation, Cancer

[ J.E. Dumont, V. Detours ,C. Maenhaut , P. Roger, P. Heimann ]

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.