Involvement of kinesin family member 2C/mitotic centromere-associated kinesin overexpression in mammary carcinogenesis.

Abstract

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.

• Authors: Arata Shimo, Chizu Tanikawa, Toshihiko Nishidate, Meng-Lay Lin, Koichi Matsuda, Jae-Hyun Park, Tomomi Ueki, Tomohiko Ohta, Koichi Hirata, Mamoru Fukuda, Yusuke Nakamura, Toyomasa Katagiri
• Journal: Cancer science (Cancer Sci) Vol. 99 Issue 1 Pg. 62-70 (Jan 2008) ISSN: 1349-7006 [Electronic] England
• PMID: 17944972 (Publication Type: Journal Article)

Chemical References

• KIF2C protein, human
• RNA, Small Interfering
• TP53 protein, human
• Tumor Suppressor Protein p53
• Kinesins

Topics

• Breast Neoplasms (enzymology, genetics, pathology)
• Cell Cycle (physiology)
• Cell Growth Processes (physiology)
• Cell Line, Tumor
• DNA Damage
• Genes, Tumor Suppressor
• Genes, p53
• HCT116 Cells
• Humans
• Immunohistochemistry
• Kinesins (biosynthesis, genetics)
• RNA, Small Interfering (genetics)
• Tumor Suppressor Protein p53 (biosynthesis, genetics)