Neurologia medico-chirurgica
Online ISSN : 1349-8029
Print ISSN : 0470-8105
ISSN-L : 0470-8105
Original Articles
Expression of Nuclear Factor-κB, Tumor Necrosis Factor Receptor Type 1, and c-Myc in Human Astrocytomas
Shuji HAYASHIMasaaki YAMAMOTOYushi UENOKohichi IKEDAKoichi OHSHIMAGen-Ichiro SOMATakeo FUKUSHIMA
Author information
JOURNAL OPEN ACCESS

2001 Volume 41 Issue 4 Pages 187-195

Details
Abstract

Tumor necrosis factor receptor type 1 (TNFR1) and c-Myc are important in signal transduction in tumor necrosis factor-α (TNF-α)-induced cytotoxicity, whereas activation of nuclear factor-κB (NF-κB) protects against TNF-α-induced apoptosis. This study investigated the expression of NF-κB, TNFR1, and c-Myc in human astrocytoma tissues by reverse transcriptase-polymerase chain reaction (PCR) and immunohistochemical analysis. TNFR1 messenger ribonucleic acid (mRNA) and c-Myc mRNA were frequently expressed in malignant astrocytomas, especially in glioblastomas, compared with low-grade astrocytomas by PCR analysis. TNFR1 and c-Myc mRNAs were barely detectable in normal brain tissues. NF-κB p50 and p65 subunit mRNAs were detected in various grades of astrocytomas, with frequent expression in malignant astrocytomas. The presence of activated NF-κB was confirmed by nuclear localization in neoplastic astrocytes as determined by immunohistochemistry. Both p50 and p65 subunits were inhomogeneously expressed in neoplastic astrocytes of glioblastoma, but only in a few scattered tumor cells in low-grade astrocytoma, and almost undetectable in normal brain tissues. These results indicate that TNFR1 and c-Myc are overexpressed in malignant astrocytomas, and this may increase the cellular sensitivity to the cytotoxic action of TNF-α. NF-κB p50 and p65 were simultaneously induced and activated in malignant astrocytomas. Our results suggest that the constitutive activation of NF-κB subunits in malignant astrocytoma, especially in glioblastoma, could be associated with the resistance to TNF-α immunotherapy, and indicates new therapeutic strategies for malignant astrocytomas.

Content from these authors
© 2001 by The Japan Neurosurgical Society

This article is licensed under a Creative Commons [Attribution-NonCommercial-NoDerivatives 4.0 International] license.
https://creativecommons.org/licenses/by-nc-nd/4.0/
Previous article Next article
feedback
Top