Pećina-Šlaus Nives, Kafka Anja, Vladušić Tomislav, Pećina Hrvoje Ivan, Hrašćan Reno
Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine University of Zagreb, Zagreb, Croatia Department of Biology, School of Medicine, University of Zagreb, Zagreb, Croatia
Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine University of Zagreb, Zagreb, Croatia Department of Biology, School of Medicine, University of Zagreb, Zagreb, Croatia.
Anticancer Res. 2016 Sep;36(9):4583-94. doi: 10.21873/anticanres.11007.
BACKGROUND/AIM: Tumor suppressor gene AXIN1 is an inhibitor of Wnt signaling pathway. It down-regulates the pathway's main signaling effector molecule, beta-catenin, in an AXIN-based destruction complex. In the present study we investigated the involvement of AXIN1 in intracranial meningioma.
Loss of heterozygosity and microsatellite instability analyses were performed. The consequences of genetic changes on protein expression levels were studied in the same patients by immunohistochemistry.
Allelic deletions of AXIN1 gene were found in 21.1% of meningiomas. Microsatellite instability was also observed in 5.3% of cases. Weak or lack of AXIN1 expression was found in 21.9% of meningiomas. We found strong statistical correlations between cytoplasmic localization of AXIN1 and its weak expression and also between the simultaneous cytoplasmic and nuclear localizations and moderate and strong expression levels (p<0.000). The findings on AXIN1 were compared to concomitant expression of APC, beta-catenin and E-cadherin in the same patients by Chi-Square tests and Pearson's correlations. Analysis revealed that AXIN1 genetic changes were significantly associated to lack of the expression of APC and presence of mutant APC proteins (p<0.018). Moderate and strong cytoplasmic and nuclear AXIN1 expressions were positively correlated to strong expression of E-cadherin (p<0.05).
Our findings on genetic changes and expression levels of AXIN1 bring novel data on its involvement in meningeal brain tumors and reveal AXIN1's relation to specific Wnt molecules.
背景/目的：肿瘤抑制基因AXIN1是Wnt信号通路的抑制剂。它在基于AXIN的破坏复合物中下调该通路的主要信号效应分子β-连环蛋白。在本研究中，我们调查了AXIN1在颅内脑膜瘤中的作用。
进行杂合性缺失和微卫星不稳定性分析。通过免疫组织化学在同一患者中研究基因变化对蛋白质表达水平的影响。
在21.1%的脑膜瘤中发现AXIN1基因的等位基因缺失。在5.3%的病例中也观察到微卫星不稳定性。在21.9%的脑膜瘤中发现AXIN1表达减弱或缺失。我们发现AXIN1的细胞质定位与其弱表达之间以及同时的细胞质和细胞核定位与中等和强表达水平之间存在很强的统计学相关性（p<0.000）。通过卡方检验和皮尔逊相关性分析，将AXIN1的研究结果与同一患者中APC、β-连环蛋白和E-钙黏蛋白的伴随表达进行比较。分析显示，AXIN1基因变化与APC表达缺失和突变APC蛋白的存在显著相关（p<0.018）。中等和强的细胞质和细胞核AXIN1表达与E-钙黏蛋白的强表达呈正相关（p<0.05）。
我们关于AXIN1基因变化和表达水平的研究结果为其在脑膜脑肿瘤中的作用带来了新的数据，并揭示了AXIN1与特定Wnt分子的关系。
