| Critical role of cyclin D3 in TSH-dependent growth of thyrocytes and in hyperproliferative diseases of the thyroid gland. | |
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MedLine Citation:
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PMID: 14576819 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We report that cyclin D3 is rate limiting for G1 progression in thyroid follicular cells and that its constitutive upregulation by chronic stimulation of the TSH/cAMP pathway plays a role in human and experimental hyperproliferative diseases of the thyroid gland. These conclusions are supported by in vitro and in vivo studies. In rat thyrocytes (PC Cl 3 cells), cyclin D3 expression is enhanced in response to activation of the TSH/cAMP pathway. Interference with the expression of G1 cyclins (in particular cyclin D3) by the antisense methodology strongly reduced TSH-dependent proliferation of PC Cl 3 cells, indicating that proper progression through G1 requires cyclin D3. Accordingly, PC Cl 3 cells engineered to overexpress cyclin D3 (PC-D3 cells) show enhanced growth rate and elude hormone-dependence and contact inhibition. Using an animal experimental model of thyroid stimulation, we demonstrate that cyclin D3 is a key mediator of TSH-dependent proliferation of thyroid follicular cells also in vivo. Cyclin D3 protein levels were higher in the thyrocytes from glands of propylthiouracil-treated rats compared with control animals. The increase in cyclin D3 expression occurred after the propylthiouracil-induced increase in TSH levels and preceded the burst of cell proliferation. Finally, we found that cyclin D3 protein is expressed in a fraction of human goiters but it is strongly overexpressed in most follicular adenomas. |
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Authors:
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Maria Letizia Motti; Angelo Boccia; Barbara Belletti; Paola Bruni; Giancarlo Troncone; Letizia Cito; Mario Monaco; Gennaro Chiappetta; Gustavo Baldassarre; Lucio Palombini; Alfredo Fusco; Giuseppe Viglietto |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Oncogene Volume: 22 ISSN: 0950-9232 ISO Abbreviation: Oncogene Publication Date: 2003 Oct |
Date Detail:
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Created Date: 2003-10-24 Completed Date: 2003-12-05 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
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Languages: eng Pagination: 7576-86 Citation Subset: IM |
Affiliation:
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Dipartimento di Biologia e Patologia Cellulare e Molecolare L.Califano, Università Federico II, via S Pansini 5, 80131 Naples, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Division / drug effects Cell Line Cyclin D3 Cyclin E Cyclin-Dependent Kinases / metabolism Cyclins / metabolism* Gene Expression Regulation / drug effects Humans Protein Kinases / metabolism Rats Thyroid Diseases / metabolism*, pathology* Thyroid Gland / cytology*, drug effects*, metabolism, pathology Thyrotropin / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/CCND3 protein, human; 0/Ccnd3 protein, rat; 0/Cyclin D3; 0/Cyclin E; 0/Cyclins; 9002-71-5/Thyrotropin; EC 2.7.-/Protein Kinases; EC 2.7.1.-/histone H1 kinase; EC 2.7.11.22/Cyclin-Dependent Kinases |
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