Expression, hormonal regulation, and subcellular localization of CCAAT/enhancer-binding protein-beta in rat and human thyrocytes.
The expression pattern of CCAAT/enhancer binding protein-beta (C/EBP-beta) was investigated in thyroid cells and tissues. Translation of C/EBP-beta mRNA results in the production of two isoforms, liver-enriched transcriptional activating protein (LAP) and liver-enriched transcriptional inhibitory protein (LIP), the latter lacking the transactivation domain. We found that LAP and LIP are expressed in the rat thyroid gland and in the FRTL-5 and PCCL3 rat thyroid cell lines. Thyrotropin (TSH), insulin, and serum withdrawal from cultures of thyroid cells induced downregulation of LAP and LIP expression. Subsequent activation of the cyclic adenosine monophosphate (cAMP) and insulin signaling pathways reinduced both isoforms. Vectors expressing rat LAP and LIP were constructed to study the effect of C/EBP-beta isoforms on the activity of the sodium iodide symporter (NIS) promoter in PCCL3 cells. The cAMP-stimulated activity of the NIS promoter was decreased by overexpression of LAP, whereas LIP had no significant effect. Expression of C/EBP-beta was studied by immunohistochemistry in normal human thyroid and papillary cancer tissues. C/EBP-beta immunostaining was always restricted to the nuclei of the normal thyrocytes. In contrast, C/EBP-beta was expressed mainly in the cytoplasm of thyroid papillary carcinoma cells. These data suggest that this factor may play important roles in the regulation of thyroidspecific genes and processes, and that its functions are altered in human thyroid carcinoma.
Pomérance
Martine
M
Institut National de la Santé et de la Recherche Médicale-Université Paris XI, Faculté de Pharmacie, Châtenay-Malabry, France. martine.pomerance@cep.u-psud.fr
Mockey
Michaël
M
Young
Jacques
J
Quillard
Jeanine
J
Blondeau
Jean-Paul
JP
D000818:Animals; D001483:Base Sequence; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics* / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology
D022782:CCAAT-Enhancer-Binding Protein-beta; D017931:DNA Primers; D007328:Insulin; D012333:RNA, Messenger; D005576:Colforsin