Aberrant nuclear factor-κB activity and its participation in the growth of human malignant astrocytoma
Aberrant nuclear factor-κB activity and its participation in the growth of human malignant astrocytoma
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DOI：
10.3171/jns.2002.96.5.0909
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发表时间：
2002-05-01
影响因子：
4.1
通讯作者：
Kunanishi, T
中科院分区：
文献类型：
--
作者：
Nagai, S;Washiyama, K;Kunanishi, T
object.核因子（NF）-κ B。一种多效性转录因子，控制细胞增殖。作者研究了NF-kappaB的活性及其参与人类恶性星形细胞瘤的生长。作者分别使用电泳迁移率变动分析和免疫组织化学研究检测了人恶性星形细胞瘤细胞系和高级别星形细胞瘤组织中的NF-κ B活性。此外，作为NF-κ B和I κ B α的代表性亚基的p50和RelA的信使（m）RNA表达，其是NF-κ B的代表性抑制蛋白。采用北方印迹杂交分析星形细胞瘤细胞系中的。此外，在星形细胞瘤细胞系中的DNA合成和细胞生长的变化进行了检查后，抑制NF-κ B活性的RelA反义寡核苷酸。作者在所有星形细胞瘤细胞系和高级别星形细胞瘤组织中发现了NF-κ B活性，但在胎儿星形细胞株或正常脑组织中没有。p50的表达。RelA和IkappaB α mRNA在胎儿星形胶质细胞株和正常成人脑组织中发现，除了星形细胞瘤细胞系。这些mRNA的相对表达水平在这些细胞系、细胞株和正常组织中是相似的。RelA反义寡核苷酸可特异性降低星形细胞瘤细胞系RelA mRNA表达水平和NF-κ B活性，从而显著抑制其DNA合成和细胞生长。人类恶性星形细胞瘤细胞具有异常的NF-κ B活性，这促进了它们的生长。这种活性与p50和RelA的异常表达无关。
Object. It has been suggested that nuclear factor (NF)-kappaB. a pleiotropic transcription factor, controls cell proliferation. The authors examined NF-kappaB activity and its participation in the growth of human malignant astrocytoma.Methods. The authors examined NF-kappaB activity in human malignant astrocytoma cell lines and high-grade astro-cytoma 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-kappaB, and IkappaBalpha., which is a representative inhibitory protein of NF-kappaB. 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-kappaB activity by RelA antisense oligodeoxynucleotide. The authors found NF-kappaB 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 IkappaBalpha 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-kappaB activity in the astrocytoma cell lines, thus significantly inhibiting their DNA synthesis and cell growth.Conclusions. Human malignant astrocytoma cells have aberrant NF-kappaB activity, which promotes their growth. This activity is not associated with aberrant expression of p50 and RelA.