Differential effects of TGF-β1 on telomerase activity in thyroid carcinoma cell lines

被引：8

作者：

Lindkvist, A ^{[1
]}

Franzén, Å ^{[1
]}

Ren, ZP ^{[1
]}

Heldin, NE ^{[1
]}

Paulsson-Karlsson, Y ^{[1
]}

机构：

[1] Univ Uppsala Hosp, Dept Genet & Pathol, Rudbeck Lab, SE-75185 Uppsala, Sweden

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2005年 / 338卷 / 03期

关键词：

anaplastic thyroid carcinoma; c-Myc; hTERT promoter; p53; telomerase; TGF-beta; 1;

D O I：

10.1016/j.bbrc.2005.10.131

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1625 / 1633

页数：9

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