Clinical and biological significance of Nemo-like kinase expression in glioma

Nemo-like kinase (NLK) is an evolutionarily conserved serine/threonine kinase that suppresses the transcriptional activity of beta-catenin/T-cell factor complex through phosphorylation of T-cell factor. Wnt/beta-catenin signaling is thought to play a critical role in human carcinogenesis, so it is possible that NLK acts as a tumor suppressor by regulating the Wnt/beta-catenin pathway. In the present study we investigated NLK expression in human gliomas in order to better understand its potential value as a therapeutic target for this disease. Specimens from 70 human gliomas were subjected to immunohistochemical and western blot analysis. We found that NLK expression was directly but inversely correlated with glioma grade. A low NLK expression level was associated with poor patient outcome. We also analyzed the effect of overexpression of NLK on cell apoptosis using a cell counting kit and western blot analysis. Our results suggest that NLK induces apoptosis in glioma cells via activation of caspases. NLK may be a useful independent prognostic indicator for glioma. Gene therapeutic approaches aimed at upregulating NLK expression could be developed for treatment of glioma. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.