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

Obara, Soichi; Nakata, Masanori; Takeshima, Hideo; Katagiri, Hideki; Asano, Tomoichiro; Oka, Yoshitomo; Maruyama, Ikuro; Kuratsu, Jun-ichi

doi:10.1016/j.canlet.2003.11.020

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Volume 208, Issue 1 , Pages 115-122, 10 May 2004

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

Soichi Obara
- Faculty of Medicine, Department of Neurosurgery, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
- Faculty of Medicine, Department of Laboratory and Molecular Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
- Corresponding author. Address: Faculty of Medicine, Department of Neurosurgery, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. Tel.: +81-99-275-5437; fax: +81-99-275-2629
Masanori Nakata
- Department of Physiology, Jichi Medical School, Minamikawachi, Kawachi, Tochigi 329-0498, Japan
Hideo Takeshima
- Faculty of Medicine, Department of Neurosurgery, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
Hideki Katagiri
- Division of Molecular Metabolism and Diabetes, Department of Internal Medicine, Tohoku University Graduate School of Medicine Seiryo-machi, Sendai, 980-8574, Japan
Tomoichiro Asano
- Faculty of Medicine, Department of Internal Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
Yoshitomo Oka
- Division of Molecular Metabolism and Diabetes, Department of Internal Medicine, Tohoku University Graduate School of Medicine Seiryo-machi, Sendai, 980-8574, Japan
Ikuro Maruyama
- Faculty of Medicine, Department of Laboratory and Molecular Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
Jun-ichi Kuratsu
- Faculty of Medicine, Department of Neurosurgery, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan

Received 10 November 2003; received in revised form 12 November 2003; accepted 13 November 2003.

Abstract

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.

Keywords: Glioblastoma, ILK, PTEN, PKB/Akt-Serine 473, NS-398