Teixeira J H, Silva Pma, Faria J, Ferreira I, Duarte P, Delgado M L, Queirós O, Moreira R, Barbosa J, Lopes C A, do Amaral J B, Monteiro L S, Bousbaa H
Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, CESPU, Gandra PRD, Portugal.
Centre for Molecular and Structural Biomedicine, CBME/IBB, University of Algarve, Faro, Portugal.
Oral Dis. 2015 Sep;21(6):713-20. doi: 10.1111/odi.12335. Epub 2015 Apr 6.
BubR1 and Mad2 are central components of the mitotic checkpoint complex that inhibits anaphase onset until all chromosomes are correctly aligned at the metaphase plate. We propose to analyse the combined expression of BubR1 and Mad2 and assess its significance to oral squamous cell carcinoma (OSCC) diagnosis and prognosis.
BubR1 and Mad2 expression was assessed by real-time PCR in OSCC cell lines and in normal human oral keratinocytes, and by immunohistochemistry in 65 patients with OSCC. The results were compared regarding clinicopathological parameters, proliferative activity and survival.
BubR1 and Mad2 transcripts were overexpressed in OSCC cell lines which also exhibited attenuated spindle assembly checkpoint activity. BubR1 and Mad2 were also overexpressed in patients with OSCC. BubR1 expression was associated with advanced stages and larger tumour size in univariate analysis, and with shorter overall survival both in univariate and multivariate analysis. Mad2 overexpression was associated with that of BubR1 and, importantly, high expression of Mad2 and BubR1 was associated with increased cellular proliferation.
Our data propose a role for BubR1 and Mad2 in OSCC cellular proliferation, progression and prognosis.
BubR1和Mad2是有丝分裂检查点复合物的核心组成部分，它们会抑制后期开始，直到所有染色体在中期板上正确排列。我们建议分析BubR1和Mad2的联合表达，并评估其对口腔鳞状细胞癌（OSCC）诊断和预后的意义。
通过实时PCR在OSCC细胞系和正常人口腔角质形成细胞中评估BubR1和Mad2的表达，并通过免疫组织化学在65例OSCC患者中进行评估。将结果与临床病理参数、增殖活性和生存率进行比较。
BubR1和Mad2转录本在OSCC细胞系中过表达，这些细胞系也表现出纺锤体组装检查点活性减弱。BubR1和Mad2在OSCC患者中也过表达。在单因素分析中，BubR1表达与晚期和更大的肿瘤大小相关，在单因素和多因素分析中均与较短的总生存期相关。Mad2过表达与BubR1相关，重要的是，Mad2和BubR1的高表达与细胞增殖增加相关。
我们的数据表明BubR1和Mad2在OSCC细胞增殖、进展和预后中起作用。
