Aberrant nuclear factor-κB activity and its participation in the growth of human malignant astrocytoma

Abstract

Object. It has been suggested that nuclear factor (NF)-κB, a pleiotropic transcription factor, controls cell proliferation. The authors examined NF-κB activity and its participation in the growth of human malignant astrocytoma. Methods. The authors examined NF-κB activity in human malignant astrocytoma cell lines and high-grade astrocytoma tissues by using electrophoretic mobility shift assays and immunohistochemical studies, respectively. In addition, messenger (m)RNA expression of p50 and RelA, which are representative subunits of NF-κB, and IκBα, which is a representative inhibitory protein of NF-κB, were analyzed using Northern blot hybridization in the astrocytoma cell lines. Furthermore, alterations in DNA synthesis and cell growth in the astrocytoma cell lines were examined after inhibition of NF-κB activity by RelA antisense oligodeoxynucleotide. The authors found NF-κB activity in all astrocytoma cell lines and high-grade astrocytoma tissues that were examined, but not in the fetal astrocyte strain or in normal cerebral tissue. Expression of p50, RelA, and IκBα mRNA was found in the fetal astrocyte strain and normal adult brain tissue, in addition to the astrocytoma cell lines. The relative levels of expression of these mRNAs were similar among these cell lines, the cell strain, and normal tissue. The RelA antisense oligodeoxynucleotide specifically reduced the levels of RelA mRNA expression and NF-κB activity in the astrocytoma cell lines, thus significantly inhibiting their DNA synthesis and cell growth. Conclusions. Human malignant astrocytoma cells have aberrant NF-κB activity, which promotes their growth. This activity is not associated with aberrant expression of p50 and RelA.