Activation of epidermal growth factor receptor results in snail protein but not mRNA overexpression in endometrial cancer.
Activation of epidermal growth factor receptor results in snail protein but not mRNA overexpression in endometrial cancer.
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DOI：
10.1111/j.1582-4934.2008.00526.x
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发表时间：
2009-09
影响因子：
5.3
通讯作者：
Becker KF
中科院分区：
文献类型：
--
作者：
Hipp S;Walch A;Schuster T;Losko S;Laux H;Bolton T;Höfler H;Becker KF
E-钙粘蛋白表达减少与许多癌症的肿瘤进展相关，包括子宫内膜癌。转录因子Snail被认为是最重要的E-cadherin转录抑制因子之一;然而，其在癌组织中的调控仍不清楚。在这里，我们报告，表皮生长因子受体（EGFR）的激活导致过度表达的蜗牛，也确定了关键的下游信号分子。表皮生长因子（EGF）刺激两种子宫内膜癌细胞系导致Snail蛋白表达增加。在原发性人子宫内膜癌中，Snail蛋白表达与EGFR（Tyr 1086）的活化、磷酸化形式相关，这一点通过使用蛋白裂解物微阵列分析24种不同的信号蛋白而揭示。此外，我们观察到这些肿瘤中Snail和E-cadherin蛋白水平之间的负相关性。最有可能的是，p38 MAPK、PAK 1、AKT、ERK 1/2和GSK-3β参与EGFR下游Snail的上调。在这些肿瘤中，Snail mRNA表达与活化的EGFR没有相关性。总之，在主要的人类组织中的信号蛋白的分析提供了强有力的证据，EGFR信号参与Snail蛋白的过度表达。
Reduced E-cadherin expression is associated with tumour progression of many carcinomas, including endometrial cancers. The transcription factor Snail is known as one of the most prominent transcriptional E-cadherin repressors; its regulation in cancer tissues, however, still remains unclear. Here, we report that activation of epidermal growth factor receptor (EGFR) resulted in overexpression of Snail and also identified critical downstream signalling molecules. Stimulation of two endometrial carcinoma cell lines with epidermal growth factor (EGF) lead to an increase of Snail protein expression. In primary human endometrioid endometrial carcinomas Snail protein expression correlated with the activated, phosphorylated form of EGFR (Tyr1086) as revealed by profiling 24 different signalling proteins using protein lysate microarrays. In addition, we observed an inverse correlation between Snail and E-cadherin protein levels in these tumours. Most likely, p38 MAPK, PAK1, AKT, ERK1/2 and GSK-3β are involved in the up-regulation of Snail downstream of EGFR. Snail mRNA expression did not show a correlation with activated EGFR in these tumours. Taken together, profiling of signalling proteins in primary human tissues provided strong evidence that EGFR signalling is involved in Snail protein overexpression.