Overexpression of Aurora-A potentiates HRAS-mediated oncogenic transformation and is implicated in oral carcinogenesis

被引：94

作者：

Tatsuka, M

Sato, S

Kitajima, S

Suto, S

Kawai, H

Miyauchi, M

Ogawa, I

Maeda, M

Ota, T

Takata, T

机构：

[1] Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Regulatory Radiobiol, Minami Ku, Hiroshima 7348553, Japan

[2] Hiroshima Univ, Sch Dent, Minami Ku, Hiroshima 7348553, Japan

[3] Hiroshima Univ, Dent Hosp, Minami Ku, Hiroshima 7348553, Japan

[4] Kanazawa Med Univ, Med Res Inst, Div Mol Oncol & Virol, Kanazawa, Ishikawa 9200293, Japan

来源：

ONCOGENE | 2005年 / 24卷 / 06期

关键词：

oral cancer; susceptibility; polymorphism; Ras; Aurora-A;

D O I：

10.1038/sj.onc.1208293

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Aurora kinases are known to play a key role in maintaining mitotic fidelity, and overexpression of aurora kinases has been noted in various tumors. Overexpression of aurora kinase activity is thought to promote cancer development through a loss of centrosome or chromosome number integrity. Here we observed augmentation of G12V-mutated HRAS-induced neoplastic transformation in BALB/c 3T3 A31-1-1 cells transfected with Aurora-A. Aurora-A-short hairpin RNA (shRNA) experiments showed that the expression level of Aurora-A determines susceptibility to transformation. Aurora-A gene amplification was noted in human patients with tongue or gingival squamous carcinoma (4/11). Amplification was observed even in pathologically normal epithelial tissue taken at sites distant from the tumors in two patients with tongue cancer. However, overexpression of Aurora-A mRNA was observed only within the tumors of all patients examined (11/11). Our data indicate that Aurora-A gene amplification and overexpression play a role in human carcinogenesis, largely due to the effect of Aurora-A on oncogenic cell growth, rather than a loss of maintenance of centrosomal or chromosomal integrity.

引用

页码：1122 / 1127

页数：6

共 24 条

[1] A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers [J].

Bischoff, JR ;

Anderson, L ;

Zhu, YF ;

Mossie, K ;

Ng, L ;

Souza, B ;

Schryver, B ;

Flanagan, P ;

Clairvoyant, F ;

Ginther, C ;

Chan, CSM ;

Novotny, M ;

Slamon, DJ ;

Plowman, GD .

EMBO JOURNAL, 1998, 17 (11) :3052-3065

[2] The cellular geography of aurora kinases [J].

Carmena, M ;

Earnshaw, WC .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2003, 4 (11) :842-854

[3] Mutations of the BRAF gene in human cancer [J].

Davies, H ;

Bignell, GR ;

Cox, C ;

Stephens, P ;

Edkins, S ;

Clegg, S ;

Teague, J ;

Woffendin, H ;

Garnett, MJ ;

Bottomley, W ;

Davis, N ;

Dicks, N ;

Ewing, R ;

Floyd, Y ;

Gray, K ;

Hall, S ;

Hawes, R ;

Hughes, J ;

Kosmidou, V ;

Menzies, A ;

Mould, C ;

Parker, A ;

Stevens, C ;

Watt, S ;

Hooper, S ;

Wilson, R ;

Jayatilake, H ;

Gusterson, BA ;

Cooper, C ;

Shipley, J ;

Hargrave, D ;

Pritchard-Jones, K ;

Maitland, N ;

Chenevix-Trench, G ;

Riggins, GJ ;

Bigner, DD ;

Palmieri, G ;

Cossu, A ;

Flanagan, A ;

Nicholson, A ;

Ho, JWC ;

Leung, SY ;

Yuen, ST ;

Weber, BL ;

Siegler, HF ;

Darrow, TL ;

Paterson, H ;

Marais, R ;

Marshall, CJ ;

Wooster, R .

NATURE, 2002, 417 (6892) :949-954

[4] Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human [J].

Ewart-Toland, A ;

Briassouli, P ;

de Koning, JP ;

Mao, JH ;

Yuan, JW ;

Chan, F ;

MacCarthy-Morrogh, L ;

Ponder, BAJ ;

Nagase, H ;

Burn, J ;

Ball, S ;

Almeida, M ;

Linardopoulos, S ;

Balmain, A .

NATURE GENETICS, 2003, 34 (04) :403-412

[5] Identification of Aurora kinases as RasGAP Src homology 3 domain-binding proteins [J].

Gigoux, V ;

L'Hoste, S ;

Raynaud, F ;

Camonis, J ;

Garbay, C .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (26) :23742-23746

[6]

Goepfert TM, 2000, CURR TOP DEV BIOL, V49, P331

[7]

Goyal RK, 1999, MOL CELL BIOL, V19, P4379

[8] VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo [J].

Harrington, EA ;

Bebbington, D ;

Moore, J ;

Rasmussen, RK ;

Ajose-Adeogun, AO ;

Nakayama, T ;

Graham, JA ;

Demur, C ;

Hercend, T ;

Diu-Hercend, A ;

Su, M ;

Golec, JMC ;

Miller, KM .

NATURE MEDICINE, 2004, 10 (03) :262-267

[9] Aurora-A and an interacting activator, the LIM protein Ajuba, are required for mitotic commitment in human cells [J].

Hirota, T ;

Kunitoku, N ;

Sasayama, T ;

Marumoto, T ;

Zhang, DW ;

Nitta, M ;

Hatakeyama, K ;

Saya, H .

CELL, 2003, 114 (05) :585-598

[10]

KAKUNAGA T, 1985, TRANSF ASS EST CELL

← 1 2 3 →