High expression of BUBR1 is one of the factors for inducing DNA aneuploidy and progression in gastric cancer
High expression of BUBR1 is one of the factors for inducing DNA aneuploidy and progression in gastric cancer
复制标题
DOI：
10.1111/j.1349-7006.2009.01457.x
复制
发表时间：
2010-03-01
期刊：
影响因子：
5.7
通讯作者：
Maehara, Yoshihiko
中科院分区：
文献类型：
--
作者：
Ando, Koji;Kakeji, Yosihiro;Maehara, Yoshihiko
胃癌表现出高频率的DNA非整倍体，一种染色体不稳定的表型。有人认为纺锤体组装检查点异常与DNA非整倍体有关，但其机制尚不清楚。我们通过评估胃癌中BUBR1的表达来研究其作用机制。对九州大学附属医院外科学科116例胃癌标本的DNA倍体模式进行了分析。其中，DNA非整倍体出现在70例（60.3%）胃癌病例中。采用免疫组化方法研究了181例胃癌标本中BUBR1的表达，并采用实时RT-PCR方法研究了几种胃癌细胞系中BUBR1的表达。BUBR1高表达病例91例（50.3%），与DNA非整倍体显著相关（P < 0.05）。BUBR1高表达病例与深部浸润、淋巴结转移、肝转移及预后不良有显著相关性。在胃癌细胞系中，BUBR1高表达与DNA非整倍体有显著关系（P < 0.05）。然后转染胃癌细胞株MKN-28和SNU-1全长BUBR1，观察BUBR1表达变化的意义。BUBR1的强制表达导致倍性模式的改变和Ki-67的高表达。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非整倍体和胃癌进展的致病因素之一。（癌症科学2010；101:639-645）
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. (Cancer Sci 2010; 101: 639-645)