Open AccessInvolvement of kinesin family member 2C/mitotic centromere‐associated kinesin overexpression in mammary carcinogenesis
Author(s) -
Shimo Arata,
Tanikawa Chizu,
Nishidate Toshihiko,
Lin MengLay,
Matsuda Koichi,
Park JaeHyun,
Ueki Tomomi,
Ohta Tomohiko,
Hirata Koichi,
Fukuda Mamoru,
Nakamura Yusuke,
Katagiri Toyomasa
Publication year - 2008
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00635.x
Subject(s) - kinesin , carcinogenesis , mitosis , cancer research , biology , cancer , breast cancer , ectopic expression , cancer cell , small interfering rna , cell culture , microbiology and biotechnology , genetics , microtubule , transfection
To elucidate the molecular mechanisms of mammary carcinogenesis and discover novel therapeutic targets for breast cancer, we previously carried out genome‐wide expression profile analysis of 81 breast cancer cases by means of cDNA microarray coupled with laser microbeam microdissection of cancer cells. Among the dozens of transactivated genes, in the present study we focused on the functional significance of kinesin family member 2C ( KIF2C )/mitotic centromere‐associated kinesin ( MCAK ) in the growth of breast cancer cells. Northern blot and immunohistochemical analyses confirmed KIF2C/MCAK overexpression in breast cancer cells, and showed that it is expressed at undetectable levels in normal human tissues except the testis, suggesting KIF2C/MCAK to be a cancer–testis antigen. Western blot analysis using breast cancer cell lines revealed a significant increase in the endogenous KIF2C/MCAK protein level and its phosphorylation in G 2 /M phase. Treatment of breast cancer cells with small interfering RNA against KIF2C/MCAK effectively suppressed KIF2C/MCAK expression and inhibited the growth of the breast cancer cell lines T47D and HBC5. In addition, we found that KIF2C/MCAK expression was significantly suppressed by ectopic introduction of p53. These findings suggest that overexpression of KIF2C/MCAK might be involved in breast carcinogenesis and is a promising therapeutic target for breast cancers. ( Cancer Sci 2008; 99: 62–70)