Molecular Diagnostics
British Journal of Cancer (2007) 97, 543–549. doi:10.1038/sj.bjc.6603905 www.bjcancer.com
Published online 24 July 2007
Clinicopathological and biological significance of mitotic centromere-associated kinesin overexpression in human gastric cancer
Y Nakamura1,2,3, F Tanaka1,2, N Haraguchi1,2, K Mimori1,2, T Matsumoto1,2, H Inoue1,2, K Yanaga3 and M Mori1,2
- 1Department of Surgery and Molecular Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumibaru, Beppu 874-0838, Japan
- 2Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 4-1-8 Honcho Kawaguchi, Saitama, Japan
- 3Department of Surgery, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, Japan
Correspondence: Dr M Mori, E-mail: mmori@beppu.kyushu.ac.jp
Received 15 April 2007; Revised 28 June 2007; Accepted 28 June 2007; Published online 24 July 2007.
Abstract
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.
Keywords:
MCAK, KIF2C, gastric cancer, migration, cancer testis antigen
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