Elevated expression of protein regulator of cytokinesis 1, involved in the growth of breast cancer cells.
To elucidate molecular mechanisms of mammary carcinogenesis and discover novel therapeutic targets for breast cancer, we previously carried out a genome-wide expression profile analysis of 81 breast cancer cases by means of a combination of cDNA microarray and laser microbeam microdissection. Among the upregulated genes, we focused on the functional significance of protein regulator of cytokinesis 1 (PRC1) in the development of breast cancer. Western blot analysis using breast cancer cell lines revealed a significant increase in endogenous PRC1 levels in G(2)/M phase. Treatment of breast cancer cells with small interfering RNA against PRC1 effectively suppressed its expression and inhibited the growth of breast cancer cell lines T47D and HBC5. Furthermore, we found an interaction between PRC1 and kinesin family member 2C/mitotic centromere-associated kinesin (KIF2C/MCAK) by coimmunoprecipitation and immunoblotting using COS-7 cells, in which these molecules were introduced exogenously. These findings suggest the involvement of a PRC1-KIF2C/MCAK complex in breast tumorigenesis, and this complex should be a promising target for the development of novel treatments for breast cancer.
Shimo
Arata
A
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo 108-8639, Japan.
Nishidate
Toshihiko
T
Ohta
Tomohiko
T
Fukuda
Mamoru
M
Nakamura
Yusuke
Y
Katagiri
Toyomasa
T
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics
D018797:Cell Cycle Proteins; C091489:KIF2C protein, human; C116662:PRC1 protein, human; D034741:RNA, Small Interfering; D016547:Kinesins