Involvement of kinesin family member 2C/mitotic centromere-associated kinesin overexpression in mammary carcinogenesis
Involvement of kinesin family member 2C/mitotic centromere-associated kinesin overexpression in mammary carcinogenesis
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DOI：
10.1111/j.1349-7006.2007.00635.x
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发表时间：
2008-01-01
期刊：
影响因子：
5.7
通讯作者：
Katagiri, Toyomasa
中科院分区：
文献类型：
--
作者：
Shimo, Arata;Tanikawa, Chizu;Katagiri, Toyomasa
为了阐明乳腺癌发生的分子机制，并发现新的乳腺癌治疗靶点，我们以前进行了全基因组表达谱分析的81例乳腺癌病例的cDNA微阵列结合激光微束显微切割的癌细胞。在几十个反式激活基因中，本研究主要关注驱动蛋白家族成员2C（KIF 2C）/有丝分裂着丝粒相关驱动蛋白（MCAK）在乳腺癌细胞生长中的功能意义。北方印迹和免疫组化分析证实KIF 2C/MCAK在乳腺癌细胞中过表达，并且显示其在除睾丸之外的正常人体组织中以不可检测的水平表达，这表明KIF 2C/MCAK是癌症-睾丸抗原。使用乳腺癌细胞系的Western印迹分析显示内源性KIF 2C/MCAK蛋白水平显著增加，并且其在G（2）/M期磷酸化。用针对KIF 2C/MCAK的小干扰RNA处理乳腺癌细胞有效地抑制了KIF 2C/MCAK的表达，并抑制了乳腺癌细胞系T47 D和HBC 5的生长。此外，我们发现，KIF 2C/MCAK的表达显着抑制异位引入p53。这些结果表明，KIF 2C/MCAK的过度表达可能参与乳腺癌的发生，是一个有前途的乳腺癌治疗靶点。
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.