| Cell cycle-dependent expression of thyroid hormone receptor-beta is a mechanism for variable hormone sensitivity. | |
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MedLine Citation:
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PMID: 14767065 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Thyroid hormone receptors (TRs) are ligand-regulatable transcription factors. Currently, little is known about the expression of TRs or other nuclear hormone receptors during the cell cycle. We thus developed a stable expression system to express green fluorescent protein-TRbeta in HeLa cells under tetracycline regulation, and studied TR expression during the cell cycle by laser scanning cytometry. Only approximately 9-15% of the nonsynchronized cell population expressed TR because the majority of cells were in G(1) phase and did not express detectable amounts of TR. However, when cells were synchronized in early S phase with hydroxyurea and then released, TR expression levels increased in a cell cycle-dependent manner and peaked to 30-40% cells expressing TR at late G(2)/M phase before declining to nonsynchronized levels. Moreover, we observed a direct correlation between transcriptional activity and TR expression during the cell cycle. Similar cell cycle-dependent findings also were observed for endogenous TR in rat pituitary GH(3) cells. Last, cycloheximide studies demonstrated that the increase in TR expression was primarily due to increased translation. These novel observations of cell cycle-dependent expression of TR suggest that differential hormone sensitivity can occur during the cell cycle and may contribute to cell cycle progression during normal development and oncogenesis. |
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Authors:
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Padma Maruvada; Natalia I Dmitrieva; Joyce East-Palmer; Paul M Yen |
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Publication Detail:
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Type: Journal Article Date: 2004-02-06 |
Journal Detail:
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Title: Molecular biology of the cell Volume: 15 ISSN: 1059-1524 ISO Abbreviation: Mol. Biol. Cell Publication Date: 2004 Apr |
Date Detail:
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Created Date: 2004-03-23 Completed Date: 2004-11-10 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 9201390 Medline TA: Mol Biol Cell Country: United States |
Other Details:
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Languages: eng Pagination: 1895-903 Citation Subset: IM |
Affiliation:
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Molecular Regulation and Neuroendocrinology Section, Clinical Endocrinology Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Cell Cycle Cell Nucleus / metabolism Cell Separation Cycloheximide / pharmacology Dose-Response Relationship, Drug Doxycycline / pharmacology Flow Cytometry G1 Phase G2 Phase Gene Expression Regulation Green Fluorescent Proteins Hela Cells Hormones / metabolism Humans Hydroxyurea / pharmacology Lasers Ligands Luminescent Proteins / metabolism Microscopy, Fluorescence Mitosis Plasmids / metabolism RNA Processing, Post-Transcriptional Rats Receptors, Thyroid Hormone / metabolism* Reverse Transcriptase Polymerase Chain Reaction S Phase Tetracycline / pharmacology Thyroid Hormone Receptors beta Time Factors Transcription, Genetic Transcriptional Activation |
| Chemical | |
Reg. No./Substance:
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0/Hormones; 0/Ligands; 0/Luminescent Proteins; 0/Receptors, Thyroid Hormone; 0/Thyroid Hormone Receptors beta; 127-07-1/Hydroxyurea; 147336-22-9/Green Fluorescent Proteins; 564-25-0/Doxycycline; 60-54-8/Tetracycline; 66-81-9/Cycloheximide |
| Comments/Corrections | |
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