The aim of the present study was to investigate the effect of transforming growth factor-beta 1 (TGF-beta 1) on telomerase activity in a panel of human anaplastic thyroid carcinoma (ATC) cell lines. Addition of TGF-beta 1 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 promotor. Addition of a PI-3 kinase inhibitor (LY294002) abrogated the stimulatory effect of TGF-beta 1 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 Initiation. In conclusion, TGF-beta 1 exerts opposing effects on telomerase activity in ATC cell lines, possibly reflecting deregulation of TGF-beta 1 signaling in a more malignant genotype. (c) 2005 Elsevier Inc. All rights reserved.