New Insights into the Role of BubR1 in Mitosis and Beyond - International Review of Cell and Molecular Biology - page 257

BubR1 mRNA compared with matched normal controls ( Grabsch et al.,
2003 ). Similarly, two studies reported that BubR1 was overexpressed in
ulcerative colitis-associated colorectal cancer and bladder cancer, respec-
tively, and that high expression of BubR1 was correlated with advanced
pathological stage, tumor recurrence, and disease progression ( Burum-
Auensen et al., 2007; Yamamoto et al., 2007 ). Moreover, 50% of gastric can-
cer samples in one study showed high expression of BubR1 ( Ando et al.,
2010 ). Human Mad2 and BubR1 mRNA level analysis were coordinately
overexpressed in 21 patients with esophageal squamous cell carcinoma ana-
lyzed by RT-PCR ( Tanaka et al., 2008 ). mRNA and protein levels for
BubR1 were found highly expressed in high-grade primary breast cancer
tissues ( Yuan et al., 2006 ). High expression of BubR1 in gastric cancer
was significantly correlated with lymph node metastasis, liver metastasis,
and poor prognosis, suggesting that BubR1 may contribute to the progres-
sion of gastric cancer ( Ando et al., 2010 ). Moreover, overexpression of
BubR1, found in 207 out of 458 cases of HCC, was also associated with
advanced pathological stage and poor overall survival ( Liu et al., 2009 ). In
addition, higher expression of BubR1 was found to correlate with shorter
survival in more than 70% of the 70 cases of oral squamous cell carcinoma
analyzed ( Lira et al., 2010 ). Immunochemistry analysis of 160 epithelial
ovarian carcinomas revealed that a high level of BubR1 was correlated with
poor prognosis, cancer aggression, and poor survival rate ( Lee et al., 2009b ).
Similarly, immunochemistry analysis using tissue microarrays showed that
BubR1 protein was overexpressed in pancreatobiliary-type tumors and
highly correlated with poor prognosis ( Gladhaug et al., 2010 ). Microarray
analysis of adrenocortical tumors revealed that combined expression of
BubR1 and PINK1 (PTEN-inducible putative kinase 1, a mitochondrial
serine threonine kinase thought to protect cells from stress-induced mito-
chondrial dysfunction), was the best predictor marker of patient survival
( de Reynies et al., 2009 ). Meta-analysis of hundreds of microarray profiles
of 771 gliomas and a few normal brain tissues that had previously been used
successfully to predict survival time in gliomas showed that high BubR1
RNA expression correlated with advanced gliomas grade and poor survival
time ( Bie et al., 2011 ).
Overexpression of BubR1 may be associated with the increased capacity
of tumor cells to proliferate since BubR1 is known to be highly expressed
during cell division. Alternatively, overexpression of BubR1 could some-
how contribute to defective SAC and genomic instability. The support
for this comes from the observation that overexpression of Mad2 in mice