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.
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.
Obara
Soichi
S
Department of Physiology, Jichi Medical School, Minamikawachi, Kawachi, Tochigi 329-0498, Japan. sochian@ta2.so-net.ne.jp
Nakata
Masanori
M
Takeshima
Hideo
H
Katagiri
Hideki
H
Asano
Tomoichiro
T
Oka
Yoshitomo
Y
Maruyama
Ikuro
I
Kuratsu
Jun-Ichi
J
D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005909:Glioblastoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D006801:Humans; D015151:Immunoblotting; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000494:pharmacology*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D013449:Sulfonamides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000099200:Scaffold Protein ILK
D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D010744:Phosphoric Monoester Hydrolases; D011451:Prostaglandin-Endoperoxide Synthases; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D013449:Sulfonamides; D000099200:Scaffold Protein ILK; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C496540:PTGS2 protein, human; C494918:AKT1 protein, human