TY - JOUR
T1 - Clinicopathological and biological significance of mitotic centromere-associated kinesin overexpression in human gastric cancer
AU - Nakamura, Y.
AU - Tanaka, F.
AU - Haraguchi, N.
AU - Mimori, K.
AU - Matsumoto, T.
AU - Inoue, H.
AU - Yanaga, K.
AU - Mori, M.
N1 - Funding Information:
We thank Dr Linda Wordeman (Moore and Wordeman, 2004), University of Washington School of Medicine (Seattle, WA, USA) for kindly providing the MCAK gene expressing vector (EGFP-HsMCAK). We thank Drs K Ieta, S Hirasaki, Y Kosaka, T Yokoe, Z Xiang, and A Sasaki for critical reading of the paper. We also thank Ms T Shimooka, Ms K Ogata, Ms M Oda, Ms N Kasagi, and Ms Y Nakagawa for their excellent technical assistance. This work was supported by the following grant sponsors: CREST, Japan Science and Technology Agency (JST); Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research, Grant nos. 17109013, 17591411, 17591413, 18390367, 18590333, 18659384, and 18790964; The Ministry of Education, Culture, Sports, Science and Technology (MEXT) Grant-in-Aid for Scientific Research on Priority Areas, Grant no. 18015039; Third Term Comprehensive Ten-year Strategy for Cancer Control, Grant no. 16271201.
PY - 2007/8/14
Y1 - 2007/8/14
N2 - Mitotic centromere-associated kinesin (MCAK) is a microtubule (MT) depolymerase necessary for ensuring proper kinetochore MT attachment during spindle formation. To determine MCAK expression status and its clinicopathological significance, real-time reverse transcriptase-polymerase chain reaction was used in 65 cases of gastric cancer. MCAK gene expression in cancer tissue was significantly higher than expression in non-malignant tissue (P<0.05). Elevated MCAK expression was significantly associated with lymphatic invasion (P=0.01) and lymph node metastasis (P=0.04). Furthermore, patients with high MCAK expression had a significantly poorer survival rate than those with low MCAK expression (P=0.008). Immunohistochemical study revealed that expression of MCAK was primarily observed in cancer cells. Additionally, a gastric cancer cell line (AZ521) that stably expressed MCAK was established and used to investigate the biological effects of the MCAK gene. In vitro results showed that cells transfected with MCAK had a high rate of proliferation (P<0.001) and increased migratory ability (P<0.001) compared to mock-transfected cells. This study demonstrated that elevated expression of MCAK may be associated with lymphatic invasion, lymph node metastasis, and poor prognosis. These characteristics may be due in part to the increased proliferative and migratory ability of cells expressing MCAK.
AB - Mitotic centromere-associated kinesin (MCAK) is a microtubule (MT) depolymerase necessary for ensuring proper kinetochore MT attachment during spindle formation. To determine MCAK expression status and its clinicopathological significance, real-time reverse transcriptase-polymerase chain reaction was used in 65 cases of gastric cancer. MCAK gene expression in cancer tissue was significantly higher than expression in non-malignant tissue (P<0.05). Elevated MCAK expression was significantly associated with lymphatic invasion (P=0.01) and lymph node metastasis (P=0.04). Furthermore, patients with high MCAK expression had a significantly poorer survival rate than those with low MCAK expression (P=0.008). Immunohistochemical study revealed that expression of MCAK was primarily observed in cancer cells. Additionally, a gastric cancer cell line (AZ521) that stably expressed MCAK was established and used to investigate the biological effects of the MCAK gene. In vitro results showed that cells transfected with MCAK had a high rate of proliferation (P<0.001) and increased migratory ability (P<0.001) compared to mock-transfected cells. This study demonstrated that elevated expression of MCAK may be associated with lymphatic invasion, lymph node metastasis, and poor prognosis. These characteristics may be due in part to the increased proliferative and migratory ability of cells expressing MCAK.
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U2 - 10.1038/sj.bjc.6603905
DO - 10.1038/sj.bjc.6603905
M3 - Article
C2 - 17653072
AN - SCOPUS:34547882734
SN - 0007-0920
VL - 97
SP - 543
EP - 549
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 4
ER -
