Department of Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Cancer Sci. 2010 Mar;101(3):639-45. doi: 10.1111/j.1349-7006.2009.01457.x. Epub 2009 Dec 4.
Gastric cancers show high frequency of DNA aneuploidy, a phenotype of chromosomal instability. It is suggested that the abnormal spindle assembly checkpoint is involved in DNA aneuploidy, but the underlying mechanism is still unclear. We studied the mechanism by assessing the expression of BUBR1 in gastric cancer. The DNA ploidy patterns of 116 gastric cancer samples obtained from the Department of Surgery and Science at Kyushu University Hospital were analyzed. Of those, DNA aneuploidy was seen in 70 (60.3%) cases of gastric cancer. The expression of BUBR1 was studied by immunohistochemistry in 181 gastric cancer samples and by real-time RT-PCR in several gastric cancer cell lines. Ninety-one (50.3%) cases had high expression of BUBR1 and those cases correlated significantly with DNA aneuploidy (P < 0.05). Also high expression of BUBR1 cases had significant correlation with deep invasion, lymph node metastasis, liver metastasis, and poor prognosis. In gastric cancer cell lines, high expression of BUBR1 had a significant relationship with DNA aneuploidy (P < 0.05). Then, gastric cancer cell lines MKN-28 and SNU-1 were transfected with full-length BUBR1 to observe the significance of the change in BUBR1 expression. Enforced expression of BUBR1 resulted in changes to the ploidy pattern and high Ki-67 expression. Collectively, our clinical and in vitro data indicate that high expression of BUBR1 may be one of causative factors for the induction of DNA aneuploidy and progression of gastric cancer.
胃癌表现出高频的 DNA 非整倍性，这是染色体不稳定性的表型。有人认为异常纺锤体组装检查点参与了 DNA 非整倍性，但潜在的机制仍不清楚。我们通过评估胃癌中 BUBR1 的表达来研究其机制。我们分析了九州大学医院外科和科学系获得的 116 个胃癌样本的 DNA 倍性模式。其中，70 例（60.3%）胃癌存在 DNA 非整倍性。我们通过免疫组织化学在 181 例胃癌样本中研究了 BUBR1 的表达，并在几种胃癌细胞系中通过实时 RT-PCR 进行了研究。91 例（50.3%）病例 BUBR1 高表达，这些病例与 DNA 非整倍性显著相关（P < 0.05）。BUBR1 高表达病例也与浸润深度、淋巴结转移、肝转移和预后不良显著相关。在胃癌细胞系中，BUBR1 的高表达与 DNA 非整倍性显著相关（P < 0.05）。然后，用全长 BUBR1 转染胃癌细胞系 MKN-28 和 SNU-1，观察 BUBR1 表达变化的意义。BUBR1 表达的强制表达导致了倍性模式的改变和高 Ki-67 表达。总之，我们的临床和体外数据表明，BUBR1 的高表达可能是诱导 DNA 非整倍性和胃癌进展的原因之一。
