YB-1 provokes breast cancer through the induction of chromosomal instability that emerges from mitotic failure and centrosome amplification

被引：120
作者：
Bergmann, S
Royer-Pokora, B
Fietze, E
Jürchott, K
Hildebrandt, B
Trost, D
Leenders, F
Claude, JC
Theuring, F
Bargou, R
Dietel, M
Royer, HD
机构：
[1] Ctr Adv European Studies & Res, D-53175 Bonn, Germany
[2] Humboldt Univ, Max Delbruck Ctr Mol Med, Inst Pathol, Fac Med, Berlin, Germany
[3] Humboldt Univ, Inst Pharmacol & Toxicol, Fac Med, Berlin, Germany
[4] Humboldt Univ, Dept Hematol Oncol & Tumorimmunol, Robert Rossle Canc Ctr, Berlin, Germany
[5] Humboldt Univ, Max Delbruck Ctr Mol Med, Helios Clin, Charite, Berlin, Germany
[6] Univ Dusseldorf, Inst Human Genet & Anthropol, D-4000 Dusseldorf, Germany
[7] German Canc Res Ctr, Div Clin Epidemiol, D-6900 Heidelberg, Germany
来源：
CANCER RESEARCH | 2005年 / 65卷 / 10期
关键词：
D O I：
10.1158/0008-5472.CAN-04-4056
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
YB-1 protein levels are elevated in most human breast cancers, and high YB-1 levels have been correlated with drug resistance and poor clinical outcome. YB-1 is a stress-responsive, cell cycle-regulated transcription factor with additional functions in RNA metabolism and translation. In this study, we show in a novel transgenic mouse model that human hemagglutinin-tagged YB-1 provokes remarkably diverse breast carcinomas through the induction of genetic instability that emerges from mitotic failure and centrosome amplification. The increase of centrosome numbers proceeds during breast cancer development and explanted tumor cell cultures show the phenotype of ongoing numerical chromosomal instability. These data illustrate a mechanism that might contribute to human breast cancer development.
引用
收藏
页码：4078 / 4087
页数：10
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