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

Abstract

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 fulllength 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)

Expression profiling of 519 kinase genes in matched malignant peripheral nerve sheath tumor/plexiform neurofibroma samples is discriminatory and identifies mitotic regulators BUB1B, PBK and NEK2 as overexpressed with transformation

“…All three of these kinases have recently been shown to have a role in other malignancies and are interesting candidates for genes in the context of the malignant transformation of plexiform neurofibromas: BUB1B and BUB1 are part of the spindle assembly checkpoint that ensures proper segregation of the chromosomes. [36][37][38][39] Alterations in BUB1B have been documented in a number of cancers including breast cancer, lung cancer, colon cancer and gastric cancer. 37,38,[40][41][42][43][44] In these, BUB1B overexpression appears associated with more aggressive behavior, increased proliferative activity, genomic complexity, chromosomal instability and DNA aneuploidy.…”

“…[36][37][38][39] Alterations in BUB1B have been documented in a number of cancers including breast cancer, lung cancer, colon cancer and gastric cancer. 37,38,[40][41][42][43][44] In these, BUB1B overexpression appears associated with more aggressive behavior, increased proliferative activity, genomic complexity, chromosomal instability and DNA aneuploidy. 37,[40][41][42][43]45,46 Interestingly, aneuploidy and complex karyotype are common finding in malignant peripheral nerve sheath tumors.…”

Integrated Analysis of Multiple Gene Expression Profiling Datasets Revealed Novel Gene Signatures and Molecular Markers in Nasopharyngeal Carcinoma

“…Several of the dysregulated genes identified in 5 and more studies, such as MAD2L1 GJA1 ( BUB1B, a member of the BUB (budding uninhibited by benzimidazole) gene family, is one of the key molecules in the spindle assembly checkpoint. High expression of BUB1B has often been reported in several malignancies and correlated with chromosomal instability (43,44). In this study, our results showed for the first time that BUB1B protein was upregulated in NPC compared with chronic inflammation of nasopharyngeal mucosa and normal adjacent epithelia of NPC, and that the high expression of BUB1B was associated with the prognosis of NPC patients.…”

The Expression of <b><i>CCAT2</i></b>, a Novel Long Noncoding RNA Transcript, and rs6983267 Single-Nucleotide Polymorphism Genotypes in Colorectal Cancers

“…Microsatellite analysis was performed using fluorescent-labeled primers and an automated DNA sequencer as previously described [16,17,20,22]. Briefly, genomic DNA isolated from cancerous and corresponding noncancerous tissue specimens was used to amplify microsatellite loci by PCR using primer sets labeled with the fluorescent compounds, 6-carboxy-X-rhodamine or 6-carboxy-20,40,70,4,7,-hexachloro-fluorescein.…”

“…CCAT2 expression was evaluated using the Fast SYBR Green Master Mix PCR Kit (Life Technologies), and transcript levels were normalized to those of β-actin as an endogenous control. The oligodeoxynucleotide primers were as follows: CCAT2 , 5′-CCCTGGTCAAATTGCTTAACCT-3′ (forward) and 5′-TTATTCGT- CCCTTTTTATGGAT-3′ (reverse) and β-actin, 5′-CCACGAAACTACCTTCAAC-3′ (forward) and 5′-GATCTTCATTGTGCTGGG-3′ (reverse) [20,21]. …”