Shigeishi Hideo, Yoneda Shingo, Taki Masayuki, Nobumori Takeshi, Ohta Kouji, Higashikawa Koichiro, Yasui Wataru, Kamata Nobuyuki
Division of Cervico-Gnathostomatology, Department of Oral and Maxillofacial Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
Oncol Rep. 2006 Apr;15(4):933-8.
Human Bub1 plays an important role at the spindle assembly check-point to prevent cell cycle progression following spindle damage. We examined the expression of Bub1 mRNA and protein in 21 human salivary gland tumors (7 pleomorphic adenomas, 2 warthin tumors, 5 mucoepidermoid carcinomas, 3 adenoid cystic carcinomas and 4 acinic cell carcinomas) and 3 normal submandibular glands using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) or western blotting. The mean expression levels of Bub1 mRNA and protein were higher in malignant tumors (0.12+/-0.028/1.75+/-0.53) than normal submandibular glands (0.042+/-0.014/0.19+/-0.044) and benign tumors (0.058+/-0.01/0.97+/-0.44). We found a significant association between the level of Bub1 mRNA/protein expression and clinical stage in malignant tumors (Mann-Whitney U test, p=0.019/p=0.016). We analyzed its relation with the proliferative activity monitored by the Ki-67 labeling index by immunohistochemistry as well as the expression of proliferating cell nuclear antigen (PCNA) by Western blotting. A significant correlation was found between Bub1 mRNA/protein expression and the Ki-67 labeling index in salivary gland tumors (Spearman's correlation coefficient by rank test, p=0.026/p=0.002). These results indicate that increased expression of the human Bub1 gene is closely linked to abnormal cell proliferation in malignant conditions.
人类Bub1在纺锤体组装检查点发挥重要作用，以防止纺锤体损伤后细胞周期进程。我们使用实时定量逆转录聚合酶链反应（RT-PCR）或蛋白质免疫印迹法检测了21例人类唾液腺肿瘤（7例多形性腺瘤、2例沃辛瘤、5例黏液表皮样癌、3例腺样囊性癌和4例腺泡细胞癌）及3例正常下颌下腺中Bub1 mRNA和蛋白的表达。恶性肿瘤中Bub1 mRNA和蛋白的平均表达水平（0.12±0.028/1.75±0.53）高于正常下颌下腺（0.042±0.014/0.19±0.044）和良性肿瘤（0.058±0.01/0.97±0.44）。我们发现恶性肿瘤中Bub1 mRNA/蛋白表达水平与临床分期之间存在显著相关性（曼-惠特尼U检验，p=0.019/p=0.016）。我们通过免疫组织化学分析了其与Ki-67标记指数监测的增殖活性以及蛋白质免疫印迹法检测的增殖细胞核抗原（PCNA）表达之间的关系。在唾液腺肿瘤中，Bub1 mRNA/蛋白表达与Ki-67标记指数之间存在显著相关性（秩和检验的Spearman相关系数，p=0.026/p=0.002）。这些结果表明，人类Bub1基因表达增加与恶性状态下的异常细胞增殖密切相关。
