Differential effects of TGF-β1 on telomerase activity in thyroid carcinoma cell lines
| Autor: | Nils-Erik Heldin, Ylva Paulsson-Karlsson, Zhi-Ping Ren, Åsa Franzén, Anna Lindkvist |
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| Rok vydání: | 2005 |
| Předmět: |
Telomerase
Genotype Transcription Genetic Biophysics Down-Regulation Biochemistry Proto-Oncogene Proteins c-myc Transforming Growth Factor beta1 Phosphatidylinositol 3-Kinases chemistry.chemical_compound Downregulation and upregulation Transforming Growth Factor beta Cell Line Tumor Humans Telomerase reverse transcriptase LY294002 RNA Messenger Thyroid Neoplasms Promoter Regions Genetic Protein Kinase Inhibitors Molecular Biology Phosphoinositide-3 Kinase Inhibitors Mitogen-Activated Protein Kinase Kinases biology Kinase Cell Biology Transforming growth factor beta Molecular biology chemistry Cell culture Mutation Cancer research biology.protein Phosphorylation Tumor Suppressor Protein p53 |
| Zdroj: | Biochemical and Biophysical Research Communications. 338:1625-1633 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2005.10.131 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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