title: MYBBP1A suppresses breast cancer tumorigenesis by enhancing the p53 dependent anoikis.
abstract: BACKGROUND
  Tumor suppressor p53 is mutated in a wide variety of human cancers and plays a critical role in anoikis, which is essential for preventing tumorigenesis. Recently, we found that a nucleolar protein, Myb-binding protein 1a (MYBBP1A), was involved in p53 activation. However, the function of MYBBP1A in cancer prevention has not been elucidated.
  
  
  METHODS
  Relationships between MYBBP1A expression levels and breast cancer progression were examined using patient microarray databases and tissue microarrays. Colony formation, xenograft, and anoikis assays were conducted using cells in which MYBBP1A was either knocked down or overexpressed. p53 activation and interactions between p53 and MYBBP1A were assessed by immunoprecipitation and western blot.
  
  
  RESULTS
  MYBBP1A expression was negatively correlated with breast cancer tumorigenesis. In vivo and in vitro experiments using the breast cancer cell lines MCF-7 and ZR-75-1, which expresses wild type p53, showed that tumorigenesis, colony formation, and anoikis resistance were significantly enhanced by MYBBP1A knockdown. We also found that MYBBP1A binds to p53 and enhances p53 target gene transcription under anoikis conditions.
  
  
  CONCLUSIONS
  These results suggest that MYBBP1A is required for p53 activation during anoikis; therefore, it is involved in suppressing colony formation and the tumorigenesis of breast cancer cells. Collectively, our results suggest that MYBBP1A plays a role in tumor prevention in the context of p53 activation.
authors: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki, 305-8577, Japan.
authors: Kensuke
authors: K
authors: Akaogi
authors: Wakana
authors: W
authors: Ono
authors: Yuki
authors: Y
authors: Hayashi
authors: Hiroyuki
authors: H
authors: Kishimoto
authors: Junn
authors: J
authors: Yanagisawa
mesh_terms: D000107:Acetylation; D000818:Animals; D023102:Anoikis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D049109:Cell Proliferation; D004268:DNA-Binding Proteins; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047468:Immunoprecipitation; D061986:MCF-7 Cells; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins; D013997:Time Factors; D046888:Tissue Array Analysis; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C491719:MYBBP1A protein, human; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins
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