[New regulation mechanisms of cell cycle shown by analysis of thyroid cell proliferation stimulated by TSH and cyclic AMP]

Abstract

In thyroid gland, different tumor types are associated with the oncogenic activation of distinct mitogenic cascades, which are normally activated either by TSH via cAMP or by growth factors. In primary cultures of thyroid cells, the cAMP-dependent mitogenic pathway, which is associated with an increased differentiation expression, does not involve most of the intermediates of the classical signalling pathways of growth factors. Especially, we have shown that TSH and cAMP trigger and support cell cycle progression, but they do not upregulate D-type cyclins and they paradoxically increase the accumulation of the CDK inhibitor p27kip1. Instead, cAMP phosphorylates and inactivates pRb by inducing the assembly and nuclear translocation of the cyclin D3-CDK4-p27 holoenzyme, and then by stimulating the activating phosphorylation of CDK4 within this complex.