| Differential effects of TGF-beta1 on telomerase activity in thyroid carcinoma cell lines. | |
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MedLine Citation:
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PMID: 16288728 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The aim of the present study was to investigate the effect of transforming growth factor-beta1 (TGF-beta1) on telomerase activity in a panel of human anaplastic thyroid carcinoma (ATC) cell lines. Addition of TGF-beta1 decreased the telomerase activity in HTh 74 and KTC-1 cells, while in C 643 and HTh 7 an increased activity was observed. The decreased telomerase activity appeared to be due to transcriptional repression of the hTERT promoter. Addition of a PI-3 kinase inhibitor (LY294002) abrogated the stimulatory effect of TGF-beta1 on the telomerase activity, indicating the possible involvement of hTERT activation via phosphorylation. Furthermore, the MEK-inhibitor U0126 had similar effects suggesting dual regulatory mechanisms. Interestingly, the cell lines differed genetically in that ATC cell lines responding with increased telomerase activity harbored a p53 mutation. In conclusion, TGF-beta1 exerts opposing effects on telomerase activity in ATC cell lines, possibly reflecting deregulation of TGF-beta1 signaling in a more malignant genotype. |
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Authors:
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Anna Lindkvist; Asa Franzén; Zhi-Ping Ren; Nils-Erik Heldin; Ylva Paulsson-Karlsson |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2005-11-02 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 338 ISSN: 0006-291X ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2005 Dec |
Date Detail:
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Created Date: 2005-11-18 Completed Date: 2006-01-06 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 1625-33 Citation Subset: IM |
Affiliation:
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Department of Genetics and Pathology, Uppsala University Hospital, Rudbeck Laboratory, SE-751 85 Uppsala, Sweden. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 3-Kinase
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antagonists & inhibitors,
metabolism Cell Line, Tumor Down-Regulation / drug effects Genotype Humans Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors, metabolism Mutation / genetics Promoter Regions, Genetic / genetics Protein Kinase Inhibitors / pharmacology Proto-Oncogene Proteins c-myc / genetics RNA, Messenger / genetics, metabolism Telomerase / genetics, metabolism* Thyroid Neoplasms / enzymology*, genetics, metabolism Transcription, Genetic / drug effects, genetics Transforming Growth Factor beta / pharmacology* Transforming Growth Factor beta1 Tumor Suppressor Protein p53 / genetics |
| Chemical | |
Reg. No./Substance:
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0/MYC protein, human; 0/Protein Kinase Inhibitors; 0/Proto-Oncogene Proteins c-myc; 0/RNA, Messenger; 0/TGFB1 protein, human; 0/Transforming Growth Factor beta; 0/Transforming Growth Factor beta1; 0/Tumor Suppressor Protein p53; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.12.2/Mitogen-Activated Protein Kinase Kinases; EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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