title: Reciprocal negative regulation between thyrotropin/3',5'-cyclic adenosine monophosphate-mediated proliferation and caveolin-1 expression in human and murine thyrocytes.
abstract: The expression of caveolins is down-regulated in tissue samples of human thyroid autonomous adenomas and in the animal model of this disease. Because several cell types present in thyroid express caveolins, it remained unclear if this down-regulation occurs in thyrocytes and which are the mechanism and role of this down-regulation in the tumor context. Here we show that prolonged stimulation of isolated human thyrocytes by TSH/cAMP/cAMP-dependent protein kinase inhibits caveolins' expression. The expression of caveolins is not down-regulated by activators of other signaling pathways relevant to thyroid growth/function. Therefore, the down-regulation of caveolins' expression in autonomous adenomas is a direct consequence of the chronic activation of the TSH/cAMP pathway in thyrocytes. The down-regulation of caveolin-1 occurs at the mRNA level, with a consequent protein decrease. TSH/cAMP induces a transcription-dependent, translation-independent destabilization of the caveolin-1 mRNA. This effect is correlated to the known proliferative role of that cascade in thyrocytes. In vivo, thyrocytes of caveolin-1 knockout mice display enhanced proliferation. This demonstrates, for the first time, the in vivo significance of the specific caveolin-1 down-regulation by one mitogenic cascade and its relation to a human disease.
authors.affiliation: Institut de Recherche Interdisciplinaire, Campus Erasme, Université Libre de Bruxelles, 808 Route de Lennik, Building C, 1070 Brussels, Belgium.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Costa
authors.forename: Maximin
authors.initials: M
authors.lastname: Senou
authors.forename: Fabienne
authors.initials: F
authors.lastname: Van Rode
authors.forename: Jean
authors.initials: J
authors.lastname: Ruf
authors.forename: Matteo
authors.initials: M
authors.lastname: Capello
authors.forename: Didier
authors.initials: D
authors.lastname: Dequanter
authors.forename: Philippe
authors.initials: P
authors.lastname: Lothaire
authors.forename: Chantal
authors.initials: C
authors.lastname: Dessy
authors.forename: Jacques Emile
authors.initials: JE
authors.lastname: Dumont
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Many
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Van Sande
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D051242:Caveolin 1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051243:Caveolin 2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology / Q000502:physiology*
chemical_list: D051242:Caveolin 1; D051243:Caveolin 2; D012333:RNA, Messenger; D005576:Colforsin; D013972:Thyrotropin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D002118:Calcium