Grabsch Heike I, Askham Jon M, Morrison Ewan E, Pomjanski Natalja, Lickvers Kristina, Parsons Wendy J, Boecking Alfred, Gabbert Helmut E, Mueller Wolfram
Academic Unit of Pathology, School of Medicine, University of Leeds, UK.
J Pathol. 2004 Feb;202(2):208-14. doi: 10.1002/path.1499.
During mitosis, the spindle checkpoint delays the onset of anaphase until all chromosomes have attached properly to the mitotic spindle, preventing chromosome missegregation. BUB (budding uninhibited by benzimidazole) 1 is one of the key components of this checkpoint. BUB1 mutations are rare in cancer tissues and no mutations have been identified in gastric cancer. In mice, immunodepletion of BUB1 abolished the spindle checkpoint. Thus, aberrant expression of BUB1 protein could impair mitotic checkpoint function, resulting in aneuploidy, a common phenomenon in gastric cancer. In the present study, an antibody was generated against BUB1 and its expression was studied in gastric cancer tissue sections (n = 80) by immunohistochemistry. Nuclear BUB1 expression was found in all gastric cancer cases. The proportion of tumour cells expressing BUB1 was significantly greater in diffuse-type than in intestinal-type gastric carcinoma (p < 0.001). No correlation was found between BUB1 expression and deoxyribonucleic acid (DNA) ploidy, microsatellite instability or any other histopathological parameters investigated. To the authors' knowledge, this is the first study of BUB1 protein expression in gastric cancer tissues. Different BUB1 protein expression levels in intestinal- and diffuse-type gastric cancer may provide further evidence of a potential link between different genetic pathways and morphological phenotype in gastric carcinogenesis. However, further studies are needed to establish whether there is an association between BUB1 protein expression level and mitotic spindle checkpoint function in gastric cancer.
在有丝分裂过程中，纺锤体检查点会延迟后期的开始，直到所有染色体都正确附着在有丝分裂纺锤体上，从而防止染色体错误分离。BUB（苯并咪唑不抑制的芽殖）1是该检查点的关键组成部分之一。BUB1突变在癌组织中很少见，在胃癌中尚未发现突变。在小鼠中，BUB1的免疫耗竭消除了纺锤体检查点。因此，BUB1蛋白的异常表达可能会损害有丝分裂检查点功能，导致非整倍体，这是胃癌中的常见现象。在本研究中，制备了一种针对BUB1的抗体，并通过免疫组织化学在胃癌组织切片（n = 80）中研究了其表达。在所有胃癌病例中均发现有核BUB1表达。弥漫型胃癌中表达BUB1的肿瘤细胞比例明显高于肠型胃癌（p < 0.001）。未发现BUB1表达与脱氧核糖核酸（DNA）倍体、微卫星不稳定性或所研究的任何其他组织病理学参数之间存在相关性。据作者所知，这是第一项关于胃癌组织中BUB1蛋白表达的研究。肠型和弥漫型胃癌中不同的BUB1蛋白表达水平可能为胃癌发生过程中不同遗传途径与形态学表型之间的潜在联系提供进一步证据。然而，需要进一步研究以确定胃癌中BUB1蛋白表达水平与有丝分裂纺锤体检查点功能之间是否存在关联。
