Differential effects of TGF-beta1 on telomerase activity in thyroid carcinoma cells
2005 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, Vol. 338, no 3, 1625-1633 p.Article in journal (Refereed) Published
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.
Anaplastic thyroid carcinoma, c-Myc, hTERT promoter, p53, Telomerase, TGF-β1
IdentifiersURN: urn:nbn:se:uu:diva-80318DOI: 10.1016/j.bbrc.2005.10.131PubMedID: 16288728 OAI: oai:DiVA.org:uu-80318DiVA: diva2:108232