p27Kip1 expression by contact inhibition as a prognostic index of human glioma
p27Kip1 expression by contact inhibition as a prognostic index of human glioma
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DOI：
10.1046/j.1471-4159.2000.0741393.x
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发表时间：
2000-04-01
影响因子：
4.7
通讯作者：
Yamada, K
中科院分区：
文献类型：
--
作者：
Fuse, T;Tanikawa, M;Yamada, K
人类神经胶质瘤的临床表现是多样的，从侵略性的生长和侵袭到明显的休眠;然而，这种多样性背后的分子机制在很大程度上尚未探索。在本研究中，我们表征了四种人胶质瘤细胞系，T98 G，A172，U251和NAC 6，每种细胞都具有不同的生长特性，A172和U251细胞在汇合后继续生长，而T98 G和NAC 6细胞的生长受到接触抑制。北方和western blot分析显示，在高细胞密度下，T98 G和NAC 6细胞中p27（Kip 1）细胞周期蛋白依赖性激酶抑制剂的表达在RNA和蛋白水平上均显著增强，而在A172和U251细胞中则没有。这些事实连同p27（Kip 1）的过表达引起A172和T98 G细胞中的G1期阻滞的发现表明，p27（Kip 1）的诱导代表了在高细胞密度下生长的重要决定因素。42例原发性胶质瘤的免疫组化分析显示p27蛋白水平与Ki-67增殖指数呈负相关。Kaplan-Meier曲线显示肿瘤中低水平的p27与总生存率降低相关。因此，在高细胞密度下，p27表达的调控被破坏可能在确定人脑胶质瘤的临床行为以及胶质瘤患者的预后中起重要作用。
The clinical manifestations of human glioma are known to be diverse, ranging from aggressive growth and invasion to apparent dormancy; however, the molecular mechanism underlying this diversity has been largely unexplored. In the present study, we characterized four human glioma cell lines, T98G, A172, U251, and NAC6, each of which has distinct growth properties, A172 and U251 cells continue to grow after confluency, whereas the growth of T98G and NAC6 cells is contact inhibited. Northern and western blot analyses revealed that at high cell density, the expression of p27(Kip1) cyclin-dependent kinase inhibitor was dramatically enhanced at both the RNA and the protein revels in T98G and NAC6 cells but not in A172 or U251. These facts together with the finding that overexpression of p27(Kip1) caused Gl arrest in A172 and T98G cells suggest that the induction of p27(Kip1) represents an important determinant of growth at high cell density. Immunohistochemical analyses of 42 primary gliomas revealed an inverse correlation between the level of p27 protein and the Ki-67 proliferative index. Kaplan-Meier plots demonstrated that a low level of p27 in tumors is associated with decreased overall survival. Thus, disrupted regulation of p27 expression at high cell density may play an important role in determining the clinical behavior of human gliomas as well as the prognosis for glioma patients.