title: Paradoxical accumulation of the cyclin-dependent kinase inhibitor p27kip1 during the cAMP-dependent mitogenic stimulation of thyroid epithelial cells.
abstract: In different systems, cAMP either blocks or promotes cell cycle progression in mid to late G1 phase. Dog thyroid epithelial cells in primary culture constitute a model of positive control of DNA synthesis initiation and G0-S pre-replicative phase progression by cyclic AMP (cAMP) as a second messenger for thyrotropin (TSH). We report here that TSH markedly increases the expression of p27kip1, the inhibitor of the cell cycle and cyclin-dependent kinases. This effect was prevented by the concomitant administration of the cAMP-independent mitogens, epidermal growth factor (EGF)+serum. EGF+serum also slightly inhibited the weak basal accumulation of p27kip1. Nevertheless, in the case of stimulation by TSH alone, the cAMP-dependent cell cycle progression was fully compatible with the enhanced expression of p27kip1. This observation is paradoxical since a decrease of p27kip1 is generally associated with growth stimulation in other systems, and since a similar cAMP-dependent increase of p27kip1 in macrophages has been found responsible for mid-G1 cell cycle arrest. The opposite regulation of p27kip1 in response to TSH or EGF+serum in dog thyroid epithelial cells suggests a major difference at mid to late G1 stages between cAMP-dependent and cAMP-independent mitogenic pathways.
authors.affiliation: Institute of Interdisciplinary Research, Université Libre de Bruxelles, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Depoortere
authors.forename: J E
authors.initials: JE
authors.lastname: Dumont
authors.forename: P P
authors.initials: PP
authors.lastname: Roger
mesh_terms: D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004285:Dogs; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology*; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D013972:Thyrotropin; D000242:Cyclic AMP; D018844:Cyclin-Dependent Kinases