Integrin-linked kinase (ILK) regulation of the cell viability in PTEN mutant glioblastoma and in vitro inhibition by the specific COX-2 inhibitor NS-398

被引:29
作者
Obara, S
Nakata, M
Takeshima, H
Katagiri, H
Asano, T
Oka, Y
Maruyama, I
Kuratsu, J
机构
[1] Kagoshima Univ, Fac Med, Dept Lab & Mol Med, Kagoshima 8908520, Japan
[2] Jichi Med Sch, Dept Physiol, Minami Kawachi, Tochigi 3290498, Japan
[3] Tohoku Univ, Grad Sch Med, Dept Internal Med, Div Mol Metab & Diabet, Sendai, Miyagi 9808574, Japan
[4] Univ Tokyo, Fac Med, Dept Internal Med, Bunkyo Ku, Tokyo 1138655, Japan
[5] Kagoshima Univ, Fac Med, Dept Neurosurg, Kagoshima 8908520, Japan
关键词
glioblastoma; ILK; PTEN; PKB/Akt-Serine; 473; NS-398;
D O I
10.1016/j.canlet.2003.11.020
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We report the increased activity and expression of the ILK protein in human glioblastomas and demonstrate that ILK activity is regulated by PTEN. The transfection of wild type-PTEN into the glioblastoma cell line U-251 MG altered the localization of ILK in the cell membrane: transfection with PTEN down-regulated PKB/Akt-Ser-473 phosphorylation via the inhibition of ILK-signaling. Our results suggest that ILK is critical for the PTEN-sensitive regulation of PKB/Akt-dependent cell survival. The selective COX-2 inhibitor NS-398 was found capable of down-regulating ILK and PKB/Akt phosphorylation. Our data indicate that inhibition of ILK signaling may be beneficial in the treatment of PTEN-deficient glioblastoma. (C) 2003 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:115 / 122
页数:8
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