Garcia-Rostan G, Tallini G, Herrero A, D'Aquila T G, Carcangiu M L, Rimm D L
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Cancer Res. 1999 Apr 15;59(8):1811-5.
Beta-catenin is an ubiquitously expressed cytoplasmic protein that has a crucial role in both E-cadherin-mediated cell-cell adhesion and as a downstream signaling molecule in the wingless pathway. Stabilization of beta-catenin followed by nuclear translocation and subsequent T-cell factor/lymphoid-enhancing factor-mediated transcriptional activation has been proposed as an important step in oncogenesis. Stabilization may occur through activating mutations in exon-3 at the phosphorylation sites for ubiquitination and degradation of beta-catenin. Immunohistochemical subcellular localization of beta-catenin and mutational analysis of exon-3 of the beta-catenin gene by single-strand conformational polymorphism followed by DNA sequencing was performed on 37 samples from 31 patients with anaplastic thyroid carcinoma. Immunofluorescent staining showed nuclear localization in 15 (42%) of the 36 samples examined. Nucleotide sequencing of mobility shifts detected by single-strand conformational polymorphism revealed somatic alterations in 19 (61%) of the 31 patients analyzed. We conclude that mutations in beta-catenin are common in anaplastic thyroid cancer and that they may activate transcription, as illustrated by frequent nuclear localization of the protein. These findings support the idea that beta-catenin acts as an oncogene and contributes to the highly aggressive behavior of this tumor.
β-连环蛋白是一种广泛表达的细胞质蛋白，在E-钙黏蛋白介导的细胞间黏附中起关键作用，同时也是无翅通路中的下游信号分子。β-连环蛋白的稳定化，随后的核转位以及随后的T细胞因子/淋巴增强因子介导的转录激活被认为是肿瘤发生中的重要步骤。稳定化可能通过β-连环蛋白泛素化和降解的磷酸化位点外显子3中的激活突变而发生。对31例间变性甲状腺癌患者的37个样本进行了β-连环蛋白的免疫组织化学亚细胞定位以及通过单链构象多态性随后进行DNA测序对β-连环蛋白基因外显子3进行突变分析。免疫荧光染色显示，在检查的36个样本中有15个（42%）出现核定位。通过单链构象多态性检测到的迁移率变化的核苷酸测序显示，在分析的31例患者中有19例（61%）存在体细胞改变。我们得出结论，β-连环蛋白突变在间变性甲状腺癌中很常见，并且它们可能激活转录，正如该蛋白频繁的核定位所示。这些发现支持了β-连环蛋白作为癌基因起作用并促成该肿瘤高度侵袭性行为的观点。
