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; Masanori Nakata; Hideo Takeshima; Hideki Katagiri; Tomoichiro Asano; Yoshitomo Oka; Ikuro Maruyama; Jun-Ichi Kuratsu

doi:10.1016/j.canlet.2003.11.020

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

Cancer Lett. 2004 May 10;208(1):115-22. doi: 10.1016/j.canlet.2003.11.020.

Authors

Soichi Obara¹, Masanori Nakata, Hideo Takeshima, Hideki Katagiri, Tomoichiro Asano, Yoshitomo Oka, Ikuro Maruyama, Jun-Ichi Kuratsu

Affiliation

¹ Department of Physiology, Jichi Medical School, Minamikawachi, Kawachi, Tochigi 329-0498, Japan. sochian@ta2.so-net.ne.jp

PMID: 15105053
DOI: 10.1016/j.canlet.2003.11.020

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Brain / drug effects
Brain / metabolism
Brain Neoplasms / enzymology
Brain Neoplasms / genetics
Brain Neoplasms / pathology
Cell Survival / drug effects
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors / pharmacology*
Fluorescent Antibody Technique
Gene Expression Regulation, Neoplastic / drug effects*
Glioblastoma / enzymology
Glioblastoma / genetics
Glioblastoma / pathology*
Humans
Immunoblotting
In Vitro Techniques
Isoenzymes / antagonists & inhibitors*
Membrane Proteins
Nitrobenzenes / pharmacology*
Phosphoric Monoester Hydrolases / genetics
Phosphoric Monoester Hydrolases / physiology*
Phosphorylation / drug effects
Prostaglandin-Endoperoxide Synthases
Protein Serine-Threonine Kinases / antagonists & inhibitors
Protein Serine-Threonine Kinases / metabolism*
Protein-Tyrosine Kinases / antagonists & inhibitors
Protein-Tyrosine Kinases / metabolism
Proto-Oncogene Proteins / antagonists & inhibitors
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-akt
Sulfonamides / pharmacology*
Tumor Cells, Cultured

Substances

Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Isoenzymes
Membrane Proteins
Nitrobenzenes
Proto-Oncogene Proteins
Sulfonamides
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
Cyclooxygenase 2
PTGS2 protein, human
Prostaglandin-Endoperoxide Synthases
integrin-linked kinase
Protein-Tyrosine Kinases
AKT1 protein, human
Protein Serine-Threonine Kinases
Proto-Oncogene Proteins c-akt
Phosphoric Monoester Hydrolases