Zeljko Martina, Pecina-Slaus Nives, Martic Tamara Nikuseva, Kusec Vesna, Beros Vili, Tomas Davor
Laboratory of Neuro-oncology, Croatian Institute for Brain Research, School of Medicine University of Zagreb, Zagreb, Croatia.
Front Biosci (Elite Ed). 2011 Jan 1;3(2):616-24. doi: 10.2741/e274.
The molecular mechanisms and candidate genes involved in metastasis to the brain need elucidation. In the present study brain metastases were analyzed regarding changes of E-cadherin (CDH1) and beta-catenin (CTNNB1). Loss of heterozygosity (LOH) of the CDH1 gene was detected in 42.2% of samples. The highest frequency of LOHs was observed in metastases from primary sites of lung adenocarcinoma and small cell lung cancer. Metastases from breast and colon demonstrated changes in 55.6% and 50% of cases. Downregulation of E-cadherin protein was observed in 83% of samples. Only 21.1% of samples with E-cadherin LOH had beta-catenin located in the nucleus. Image analysis showed that the quantities of E-cadherin and beta-catenin were significantly positively correlated (P = 0.008). Changes of E-cadherin were frequent in brain metastases that we investigated. Lack of mutations of beta-catenin, the fact that it was not frequently found in the nucleus and the positive correlation between the two proteins may suggest that the break-up of adherens junctions, and not the activation of wnt signaling, is responsible for metastasis formation.
转移至脑部所涉及的分子机制和候选基因有待阐明。在本研究中，分析了脑转移瘤中E-钙黏蛋白（CDH1）和β-连环蛋白（CTNNB1）的变化情况。在42.2%的样本中检测到CDH1基因杂合性缺失（LOH）。在肺腺癌和小细胞肺癌原发部位的转移瘤中观察到最高频率的LOH。来自乳腺和结肠的转移瘤分别在55.6%和50%的病例中出现变化。在83%的样本中观察到E-钙黏蛋白蛋白表达下调。在E-钙黏蛋白LOH的样本中，只有21.1%的样本β-连环蛋白定位于细胞核。图像分析显示，E-钙黏蛋白和β-连环蛋白的量呈显著正相关（P = 0.008）。在我们研究的脑转移瘤中，E-钙黏蛋白的变化很常见。β-连环蛋白缺乏突变，其在细胞核中不常被发现以及两种蛋白之间的正相关可能表明，黏附连接的破坏而非Wnt信号的激活是转移形成的原因。
