High expression of BUBR1 is one of the factors for inducing DNA aneuploidy and progression in gastric cancer

被引:82
作者
Ando, Koji [1 ]
Kakeji, Yosihiro [1 ]
Kitao, Hiroyuki [2 ]
Iimori, Makoto [2 ]
Zhao, Yan [1 ]
Yoshida, Rintaro [1 ]
Oki, Eiji [3 ]
Yoshinaga, Keiji [1 ]
Matumoto, Takuya [1 ]
Morita, Masaru [1 ]
Sakaguchi, Yoshihisa [3 ]
Maehara, Yoshihiko [1 ]
机构
[1] Kyushu Univ, Grad Sch Med Sci, Dept Surg & Sci, Fukuoka 812, Japan
[2] Kyushu Univ, Grad Sch Med Sci, Dept Mol Oncol, Fukuoka 812, Japan
[3] Kyushu Natl Canc Ctr, Fukuoka, Japan
关键词
MITOTIC CHECKPOINT GENES; PREMATURE CHROMATID SEPARATION; PROTEINS AURORA-A; SPINDLE CHECKPOINT; CHROMOSOMAL INSTABILITY; MICROSATELLITE INSTABILITY; OVEREXPRESSION; PLOIDY; BUB1B; MAD2;
D O I
10.1111/j.1349-7006.2009.01457.x
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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)
引用
收藏
页码:639 / 645
页数:7
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