title: YB-1 provokes breast cancer through the induction of chromosomal instability that emerges from mitotic failure and centrosome amplification.
abstract: 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.
authors.affiliation: Max-Delbrück Center for Molecular Medicine, Charité, Humboldt, University, Berlin, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Bergmann
authors.forename: Brigitte
authors.initials: B
authors.lastname: Royer-Pokora
authors.forename: Ellen
authors.initials: E
authors.lastname: Fietze
authors.forename: Karsten
authors.initials: K
authors.lastname: Jürchott
authors.forename: Barbara
authors.initials: B
authors.lastname: Hildebrandt
authors.forename: Detlef
authors.initials: D
authors.lastname: Trost
authors.forename: Frauke
authors.initials: F
authors.lastname: Leenders
authors.forename: Jenny-Chang
authors.initials: JC
authors.lastname: Claude
authors.forename: Franz
authors.initials: F
authors.lastname: Theuring
authors.forename: Ralf
authors.initials: R
authors.lastname: Bargou
authors.forename: Manfred
authors.initials: M
authors.lastname: Dietel
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Royer
mesh_terms: 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
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human