Differential expression of Wnt genes, β-catenin and E-cadherin in human brain tumors
Differential expression of Wnt genes, β-catenin and E-cadherin in human brain tumors
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DOI：
10.1016/s0304-3835(02)00085-x
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发表时间：
2002-09-08
期刊：
影响因子：
9.7
通讯作者：
Hong, YR
中科院分区：
文献类型：
--
作者：
Howng, SL;Wu, CH;Hong, YR
Wnt通过其下游效应子β-连环蛋白和一组在物种间很大程度上保守的其他细胞内调节因子调节发育和致癌过程。E-钙粘蛋白是一种与β-连环蛋白相关的蛋白质，在细胞间粘附中起着至关重要的作用。为进一步了解Wnt信号通路和E-cadherin在脑肿瘤发生中的分子基础，采用逆转录-聚合酶链反应（RT-PCR）方法检测了Wnt 1、Wnt 5a、Wnt 10 b和Wnt 13基因和E-cadherin在脑肿瘤中的表达。此外，还研究了它们的下游效应物β-连环蛋白。结果显示，Wnt 5a（41/45）、Wnt 10 b（37/45）和Wnt 13（35/45）在脑肿瘤中均有表达，而Wnt 1（6/45）的表达与脑肿瘤的病理分级无关。有趣的是，E-cadherin仅在少数星形细胞瘤中表达（2/16），而在大多数脑膜瘤（14/15）和垂体腺瘤中表达（12/14）。脑肿瘤中β-catenin的表达谱没有明显差异;然而，β-catenin的测序数据显示星形细胞瘤中推测的磷酸化位点S73 F和S23 G有两个突变。此外，体外功能测定显示β-连环蛋白的S73 F和S23 G突变体不影响TCF-4-荧光素酶报告基因构建体的转录活性，表明它们可能需要更复杂的因子参与星形细胞瘤。综上所述，我们的数据表明，β-catenin的突变与E-cadherin和Wnt信号可能参与脑肿瘤的发生。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
Wnt regulates developmental and oncogenic processes through its downstream effector, beta-catenin, and a set of other intracellular regulators that are largely conserved among species. E-cadherin was discovered as a protein associated with beta-catenin which plays a crucial role in cell-cell adhesion. To further understand the molecular basis of Wnt signaling pathway and E-cadherin in brain tumorigenesis, the expression of four Wnt genes (Wnt1, Wnt5a, Wnt10b and Wnt13) and E-cadherin were analyzed by reverse transcriptase-polymerase chain reaction. In addition, their downstream effector, beta-catenin, was also investigated. The results showed that the expression of Wnt5a (41/45), Wnt10b (37/45), and Wnt13 (35/45) were found in brain tumors, whereas Wnt 1 (6/45) was shown to be less related. Interestingly, E-cadherin was only expressed in a few cases of astrocytoma (2/16), whereas it was expressed in most meningioma (14/15) and pituitary adenoma tumors (12/14). There was no apparent difference of beta-catenin expression profile in brain tumors; however, the sequencing data of beta-catenin showed two mutations on speculative phosphorylation sites, S73F and S23G in astrocytoma. Furthermore, an in vitro functional assay showed that S73F and S23G mutants of beta-catenin did not affect transcriptional activity in TCF-4-leuciferase reporter construct, suggesting that they may need more complex factors to participate in astrocytoma. Taken together, our data suggest that the mutations of beta-catenin together with E-cadherin and Wnt signaling might be involved in brain tumorigenesis. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.