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

共 50 条

[1] Anaplastic thyroid carcinoma: Behavior, biology, and therapeutic approaches
Ain, KB
[J]. THYROID, 1998, 8 (08) : 715 - 726
[2] SOMATOSTATIN ANALOGS AFFECT PROLIFERATION OF HUMAN THYROID-CARCINOMA CELL-LINES IN-VITRO
AIN, KB
TAYLOR, KD
[J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1994, 78 (05) : 1097 - 1102
[3] The amino-terminal phosphorylation sites of C-MYC are frequently mutated in Burkitt's lymphoma lines but not in mouse plasmacytomas and rat immunocytomas
Axelson, H
Henriksson, M
Wang, Y
Magnusson, KP
Klein, G
[J]. EUROPEAN JOURNAL OF CANCER, 1995, 31A (12) : 2099 - 2104
[4] Extension of life-span by introduction of telomerase into normal human cells
Bodnar, AG
Ouellette, M
Frolkis, M
Holt, SE
Chiu, CP
Morin, GB
Harley, CB
Shay, JW
Lichtsteiner, S
Wright, WE
[J]. SCIENCE, 1998, 279 (5349) : 349 - 352
[5] Boldrini L, 2004, ONCOL REP, V11, P395
[6] BRENNING G, 1985, SCAND J HAEMATOL, V35, P178
[7] FORMATION AND GROWTH OF MULTICELLULAR SPHEROIDS OF HUMAN-ORIGIN
CARLSSON, J
NILSSON, K
WESTERMARK, B
PONTEN, J
SUNDSTROM, C
LARSSON, E
BERGH, J
PAHLMAN, S
BUSCH, C
COLLINS, VP
[J]. INTERNATIONAL JOURNAL OF CANCER, 1983, 31 (05) : 523 - 533
[8] Cerezo A, 2002, J CELL SCI, V115, P1305
[9] The human telomerase catalytic subunit hTERT: organization of the gene and characterization of the promoter
Cong, YS
Wen, JP
Bacchetti, S
[J]. HUMAN MOLECULAR GENETICS, 1999, 8 (01) : 137 - 142
[10] Role of transforming growth factor-β signaling in cancer
de Caestecker, MP
Piek, E
Roberts, AB
[J]. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2000, 92 (17): : 1388 - 1402

← 1 2 3 4 5 →