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TNKS1 的表达与人星形细胞瘤的病理分级和 Wnt/β-catenin 通路相关。

Expression of TNKS1 is correlated with pathologic grade and Wnt/β-catenin pathway in human astrocytomas.

机构信息

Department of Neurosurgery, Xiangya Hospital of Central South University, 87 Xiangya Road, Changsha, Hunan 410078, China.

出版信息

J Clin Neurosci. 2012 Jan;19(1):139-43. doi: 10.1016/j.jocn.2011.08.013. Epub 2011 Dec 10.

Abstract

Astrocytoma is the most common neoplasm of the central nervous system, and its malignancy is closely related to activation of the Wnt/β-catenin pathway. Accumulated evidence shows that tankyrase (TNKS) is necessary for the Wnt/β-catenin pathway, stabilizing β-catenin, and that TNKS1, a major member of the TNKS family, is involved in a wide range of human cancers. However, the expression of TNKS1 and the molecular relationship between TNKS1 and β-catenin in human astrocytomas is largely unknown. In the present study, we investigated the expression of TNKS1 in human astrocytomas using reverse transcription-polymerase chain reaction, Western blot and immunohistochemistry. The mRNA and protein expression levels of TNKS1 in astrocytomas were significantly higher compared with the normal brain tissues. Significant association between TNKS1 upregulation and pathological grade of astrocytomas was also confirmed. In addition, β-catenin immunostaining of the sampled tissues revealed a highly similar change to TNKS1. This study provides additional evidence for the involvement of TNKS1 gene and the Wnt/β-catenin signaling pathway in the genesis and progression of astrocytoma. TNKS1 may have a key role in astrocytomas.

摘要

星形细胞瘤是中枢神经系统最常见的肿瘤,其恶性程度与 Wnt/β-连环蛋白途径的激活密切相关。大量证据表明,端锚聚合酶(TNKS)是 Wnt/β-连环蛋白途径所必需的,它稳定β-连环蛋白,而 TNKS 家族的主要成员 TNKS1 参与广泛的人类癌症。然而,TNKS1 在人类星形细胞瘤中的表达以及 TNKS1 与β-连环蛋白之间的分子关系在很大程度上尚不清楚。在本研究中,我们使用逆转录-聚合酶链反应、Western blot 和免疫组织化学方法研究了 TNKS1 在星形细胞瘤中的表达。星形细胞瘤中 TNKS1 的 mRNA 和蛋白表达水平明显高于正常脑组织。还证实了 TNKS1 上调与星形细胞瘤病理分级之间存在显著相关性。此外,对采样组织的β-连环蛋白免疫染色显示出与 TNKS1 高度相似的变化。这项研究为 TNKS1 基因和 Wnt/β-连环蛋白信号通路参与星形细胞瘤的发生和发展提供了更多证据。TNKS1 可能在星形细胞瘤中具有关键作用。

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