Expression of nuclear factor-kappa B, tumor necrosis factor receptor type 1, and c-Myc in human astrocytomas.
Tumor necrosis factor receptor type 1 (TNFR1) and c-Myc are important in signal transduction in tumor necrosis factor-alpha (TNF-alpha)-induced cytotoxicity, whereas activation of nuclear factor-kappa B (NF-kappa B) protects against TNF-alpha-induced apoptosis. This study investigated the expression of NF-kappa B, 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-kappa B p50 and p65 subunit mRNAs were detected in various grades of astrocytomas, with frequent expression in malignant astrocytomas. The presence of activated NF-kappa B 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-alpha. NF-kappa B p50 and p65 were simultaneously induced and activated in malignant astrocytomas. Our results suggest that the constitutive activation of NF-kappa B subunits in malignant astrocytoma, especially in glioblastoma, could be associated with the resistance to TNF-alpha immunotherapy, and indicates new therapeutic strategies for malignant astrocytomas.
Hayashi
S
S
Department of Neurosurgery, Fukuoka University School of Medicine, Fukuoka.
Yamamoto
M
M
Ueno
Y
Y
Ikeda
K
K
Ohshima
K
K
Soma
G
G
Fukushima
T
T
D015703:Antigens, CD / Q000032:analysis*; D001254:Astrocytoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D001923:Brain Chemistry; D001932:Brain Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016233:Immunotherapy, Active; D066298:In Vitro Techniques; D016328:NF-kappa B / Q000032:analysis*; D016133:Polymerase Chain Reaction; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis*; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis*; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use
D015703:Antigens, CD; D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha