YB-1 provokes breast cancer through the induction of chromosomal instability that emerges from mitotic failure and centrosome amplification.
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.
Bergmann
Stephan
S
Max-Delbrück Center for Molecular Medicine, Charité, Humboldt, University, Berlin, Germany.
Royer-Pokora
Brigitte
B
Fietze
Ellen
E
Jürchott
Karsten
K
Hildebrandt
Barbara
B
Trost
Detlef
D
Leenders
Frauke
F
Claude
Jenny-Chang
JC
Theuring
Franz
F
Bargou
Ralf
R
Dietel
Manfred
M
Royer
Hans-Dieter
HD
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D018385:Centrosome / Q000502:physiology*; D043171:Chromosomal Instability; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins; D051840:Y-Box-Binding Protein 1
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human