Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine University of Zagreb, Salata 12, 10000, Zagreb, Croatia.
Pathol Oncol Res. 2010 Mar;16(1):75-9. doi: 10.1007/s12253-009-9190-9. Epub 2009 Jul 25.
In the present study changes of components of Wnt signaling pathway--axin (AXIN1) and beta-catenin (CTNNB1) in a sample of 72 neuroepithelial brain tumors were investigated. AXIN-1 gene was tested by PCR/loss of heterozygosity (LOH). Immunostaining and image analysis revealed the quantity and localization of relevant proteins. Polymorphic marker for AXIN-1, showed LOH in 11.1% of tumors. LOH was distributed to 6.3% of glioblastomas, one was found in neuroepithelial dysembrioplastic tumor and one in medulloblastoma. Down regulation of axin expression and up regulation of beta-catenin were detected in the analyzed tumors. Axin was observed in the cytoplasm in 68.8% of samples, in 28.1% in both the cytoplasm and nucleus and 3.1% had no expression. Beta-catenin was observed mainly in the nucleus and cytoplasm (59.4%). Expression in 34.4% of samples was in the cytoplasm and 6.3% showed no expression. Comparison of mean values of relative increase of axin and beta-catenin showed that they are significantly reversely proportional (P = 0.014). Relative quantity of beta-catenin in patients with gross deletion of AXIN1 was significantly higher in comparison to patients without LOH (P = 0.040). Our results demonstrate that changes of key components of the Wnt signaling play a role in neuroepithelial brain tumors.
在本研究中，研究了 72 例神经上皮脑肿瘤样本中 Wnt 信号通路成分——轴蛋白（AXIN1）和β-连环蛋白（CTNNB1）的变化。AXIN-1 基因通过 PCR/杂合性丢失（LOH）进行测试。免疫染色和图像分析揭示了相关蛋白的数量和定位。AXIN-1 的多态性标记物在 11.1%的肿瘤中发生 LOH。LOH 分布于 6.3%的胶质母细胞瘤中，1 例见于神经上皮发育不良性肿瘤，1 例见于髓母细胞瘤。在分析的肿瘤中检测到 axin 表达下调和β-catenin 上调。在 68.8%的样本中观察到 axin 在细胞质中，在 28.1%的样本中在细胞质和核中均有表达，而 3.1%的样本无表达。β-catenin 主要存在于细胞核和细胞质中（59.4%）。在 34.4%的样本中观察到细胞质中的表达，而 6.3%的样本无表达。axin 和β-catenin 的相对增加均值的比较表明，它们呈显著的负相关（P = 0.014）。与没有 LOH 的患者相比，AXIN1 总缺失患者的β-catenin 相对数量明显更高（P = 0.040）。我们的结果表明，Wnt 信号关键成分的变化在神经上皮脑肿瘤中起作用。
