Elevated expression of protein regulator of cytokinesis 1, involved in the growth of breast cancer cells

被引:95
作者
Shimo, Arata
Nishidate, Toshihiko
Ohta, Tomohiko
Fukuda, Mamoru
Nakamura, Yusuke
Katagiri, Toyomasa
机构
[1] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab,Minato Ku, Tokyo 1088639, Japan
[2] St Marianna Univ, Sch Med, Dept Surg, Div Breast & Endocrine Surg,Miyamae Ku, Kawasaki, Kanagawa 2168511, Japan
关键词
D O I
10.1111/j.1349-7006.2006.00381.x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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收藏
页码:174 / 181
页数:8
相关论文
共 31 条
[1]   PCOTH, a novel gene overexpressed in prostate cancers, promotes prostate cancer cell growth through phosphorylation of oncoprotein TAF-lβ/SET [J].
Anazawa, Y ;
Nakagawa, H ;
Furihara, M ;
Ashida, S ;
Tamura, K ;
Yoshioka, H ;
Shuin, T ;
Fujioka, T ;
Katagiri, T ;
Nakamura, Y .
CANCER RESEARCH, 2005, 65 (11) :4578-4586
[2]   Expression of novel molecules, MICAL2-PV (MICAL2 prostate cancer variants), increases with high Gleason score and prostate cancer progression [J].
Ashida, S ;
Furihata, M ;
Katagiri, T ;
Tamura, K ;
Anazawa, Y ;
Yoshioka, H ;
Miki, T ;
Fujioka, T ;
Shuin, T ;
Nakamura, Y ;
Nakagawa, H .
CLINICAL CANCER RESEARCH, 2006, 12 (09) :2767-2773
[3]   Human mitotic spindle-associated protein PRC1 inhibits MgcRacGAP activity toward Cdc42 during the metaphase [J].
Ban, R ;
Irino, Y ;
Fukami, K ;
Tanaka, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (16) :16394-16402
[4]   Molecular targets for breast cancer therapy and prevention [J].
Bange, J ;
Zwick, E ;
Ullrich, A .
NATURE MEDICINE, 2001, 7 (05) :548-552
[5]   KIF14 and citron kinase act together to promote efficient cytokinesis [J].
Gruneberg, U ;
Neef, R ;
Li, XL ;
Chan, EHY ;
Chalamalasetty, RB ;
Nigg, EA ;
Barr, FA .
JOURNAL OF CELL BIOLOGY, 2006, 172 (03) :363-372
[6]   SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells [J].
Hamamoto, R ;
Furukawa, Y ;
Morita, M ;
Iimura, Y ;
Silva, FP ;
Li, MH ;
Yagyu, R ;
Nakamura, Y .
NATURE CELL BIOLOGY, 2004, 6 (08) :731-740
[7]   PRC1: A human mitotic spindle-associated CDK substrate protein required for cytokinesis [J].
Jiang, W ;
Jimenez, G ;
Wells, NJ ;
Hope, TJ ;
Wahl, GM ;
Hunter, T ;
Fukunaga, R .
MOLECULAR CELL, 1998, 2 (06) :877-885
[8]  
KATHERINE NN, 2001, NAT MED, V7, P552
[9]   Expression profiles of non-small cell lung cancers on cDNA microarrays: Identification of genes for prediction of lymph-node metastasis and sensitivity to anti-cancer drugs [J].
Kikuchi, T ;
Daigo, Y ;
Katagiri, T ;
Tsunoda, T ;
Okada, K ;
Kakiuchi, S ;
Zembutsu, H ;
Furukawa, Y ;
Kawamura, M ;
Kobayashi, K ;
Imai, K ;
Nakamura, Y .
ONCOGENE, 2003, 22 (14) :2192-2205
[10]   Essential roles of KIF4 and its binding partner PRC1 in organized central spindle midzone formation [J].
Kurasawa, Y ;
Earnshaw, WC ;
Mochizuki, Y ;
Dohmae, N ;
Todokoro, K .
EMBO JOURNAL, 2004, 23 (16) :3237-3248