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Differential effects of TGF-beta1 on telomerase activity in thyroid carcinoma cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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2005 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, Vol. 338, no 3, 1625-1633 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2005. Vol. 338, no 3, 1625-1633 p.
Keyword [en]
Anaplastic thyroid carcinoma, c-Myc, hTERT promoter, p53, Telomerase, TGF-β1
Identifiers
URN: urn:nbn:se:uu:diva-80318DOI: 10.1016/j.bbrc.2005.10.131PubMedID: 16288728 OAI: oai:DiVA.org:uu-80318DiVA: diva2:108232
Available from: 2006-05-05 Created: 2006-05-05 Last updated: 2009-05-11Bibliographically approved

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Heldin, Nils-Erik

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