NMC : Vol. 41 (2001) , No. 4 187-195

Expression of Nuclear Factor-κB, Tumor Necrosis Factor Receptor Type 1, and c-Myc in Human Astrocytomas

Shuji HAYASHI¹⁾, Masaaki YAMAMOTO¹⁾²⁾, Yushi UENO¹⁾, Kohichi IKEDA¹⁾, Koichi OHSHIMA³⁾, Gen-Ichiro SOMA⁴⁾ and Takeo FUKUSHIMA¹⁾

1) Department of Neurosurgery, Fukuoka University School of Medicine
2) Molecular Oncology Center, Fukuoka University School of Medicine
3) Department of Pathology, Fukuoka University School of Medicine
4) Institute for Health Sciences, Tokushima Bunri University

(Received August 2, 2000)
(Accepted January 23, 2001)

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.

Key words:

astrocytoma, tumor necrosis factor-α immunotherapy, nuclear factor-κB