title: Implication of polycomb members Bmi-1, Mel-18, and Hpc-2 in the regulation of p16INK4a, p14ARF, h-TERT, and c-Myc expression in primary breast carcinomas.
abstract: OBJECTIVE
  Deregulation of mammalian Polycomb group (PcG) members may contribute to human carcinogenesis. p16INK4a and p14ARF tumor suppressors, human telomerase reverse transcriptase (h-TERT), and oncoprotein c-Myc have been implicated in the regulation of the cell cycle and proliferation mediated by PcG proteins, mainly Bmi-1, in mice and in cell culture experiments. Here, we examine whether these in vitro findings can be extrapolated to the in vivo situation.
  
  
  METHODS
  We measure the expression of PcG members Bmi-1, Mel-18, and Hpc-2 and their potential targets by reverse transcription-PCR, immunostaining, and Western blotting in a series of 134 breast carcinomas and correlate the data with several clinical-pathologic variables of the tumors.
  
  
  RESULTS
  Expression of PcG genes was variably detected, but overexpression of Bmi-1 was the most frequent PcG alteration observed. In addition, statistical direct correlation in expression level of the three PcG members was detected. A correlation between c-Myc and Bmi-1 expression levels was observed; however, there was no correlation between expression of Bmi-1 and p16INK4a, p14ARF, or h-TERT. However, expression of the other PcG members Mel-18 and Hpc-2 correlated with the cell cycle regulators. Moreover, PcG mRNA-altered expression correlated significantly with certain clinical-pathologic variables associated with poor prognosis.
  
  
  CONCLUSIONS
  Our data suggest that the oncogenic role of Bmi-1 in human primary breast carcinomas is not determined by its capacity to inhibit INK4a/ARF proteins or to induce telomerase activity.
authors.affiliation: Department of Medical Oncology, Hospital Universitario Puerta de Hierro, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Silva
authors.forename: José M
authors.initials: JM
authors.lastname: García
authors.forename: Cristina
authors.initials: C
authors.lastname: Peña
authors.forename: Vanesa
authors.initials: V
authors.lastname: García
authors.forename: Gemma
authors.initials: G
authors.lastname: Domínguez
authors.forename: Dolores
authors.initials: D
authors.lastname: Suárez
authors.forename: Francisca I
authors.initials: FI
authors.lastname: Camacho
authors.forename: Ruth
authors.initials: R
authors.lastname: Espinosa
authors.forename: Mariano
authors.initials: M
authors.lastname: Provencio
authors.forename: Pilar
authors.initials: P
authors.lastname: España
authors.forename: Félix
authors.initials: F
authors.lastname: Bonilla
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics / Q000378:metabolism*
chemical_list: C069077:BMI1 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; C421605:ELAC2 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C489348:PCGF2 protein, human; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D012097:Repressor Proteins; D025803:Tumor Suppressor Protein p14ARF; D063150:Polycomb Repressive Complex 1; C509186:TERT protein, human; D019098:Telomerase