title: Clinicopathologic significance of BubR1 and Mad2 overexpression in oral cancer.
abstract: OBJECTIVE
  BubR1 and Mad2 are central components of the mitotic checkpoint complex that inhibits anaphase onset until all chromosomes are correctly aligned at the metaphase plate. We propose to analyse the combined expression of BubR1 and Mad2 and assess its significance to oral squamous cell carcinoma (OSCC) diagnosis and prognosis.
  
  
  METHODS
  BubR1 and Mad2 expression was assessed by real-time PCR in OSCC cell lines and in normal human oral keratinocytes, and by immunohistochemistry in 65 patients with OSCC. The results were compared regarding clinicopathological parameters, proliferative activity and survival.
  
  
  RESULTS
  BubR1 and Mad2 transcripts were overexpressed in OSCC cell lines which also exhibited attenuated spindle assembly checkpoint activity. BubR1 and Mad2 were also overexpressed in patients with OSCC. BubR1 expression was associated with advanced stages and larger tumour size in univariate analysis, and with shorter overall survival both in univariate and multivariate analysis. Mad2 overexpression was associated with that of BubR1 and, importantly, high expression of Mad2 and BubR1 was associated with increased cellular proliferation.
  
  
  CONCLUSIONS
  Our data propose a role for BubR1 and Mad2 in OSCC cellular proliferation, progression and prognosis.
authors.affiliation: Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, CESPU, Gandra PRD, Portugal.
authors.forename: J H
authors.initials: JH
authors.lastname: Teixeira
authors.affiliation: Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, CESPU, Gandra PRD, Portugal.|Centre for Molecular and Structural Biomedicine, CBME/IBB, University of Algarve, Faro, Portugal.
authors.forename: Pma
authors.initials: P
authors.lastname: Silva
authors.affiliation: Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, CESPU, Gandra PRD, Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Faria
authors.affiliation: Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, CESPU, Gandra PRD, Portugal.
authors.forename: I
authors.initials: I
authors.lastname: Ferreira
authors.affiliation: Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, CESPU, Gandra PRD, Portugal.
authors.forename: P
authors.initials: P
authors.lastname: Duarte
authors.affiliation: Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, CESPU, Gandra PRD, Portugal.
authors.forename: M L
authors.initials: ML
authors.lastname: Delgado
authors.affiliation: Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, CESPU, Gandra PRD, Portugal.|CBMA - Center of Molecular and Environmental Biology, Department of Biology, University of Minho, Braga, Portugal.
authors.forename: O
authors.initials: O
authors.lastname: Queirós
authors.affiliation: Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, CESPU, Gandra PRD, Portugal.|CBMA - Center of Molecular and Environmental Biology, Department of Biology, University of Minho, Braga, Portugal.
authors.forename: R
authors.initials: R
authors.lastname: Moreira
authors.affiliation: Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, CESPU, Gandra PRD, Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Barbosa
authors.affiliation: Molecular Pathology and Immunology Department, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
authors.forename: C A
authors.initials: CA
authors.lastname: Lopes
authors.affiliation: Stomatology Department, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: J B
authors.initials: JB
authors.lastname: do Amaral
authors.affiliation: Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, CESPU, Gandra PRD, Portugal.
authors.forename: L S
authors.initials: LS
authors.lastname: Monteiro
authors.affiliation: Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, CESPU, Gandra PRD, Portugal.|Centro de Química Medicinal da Universidade do Porto (CEQUIMED-UP), Porto, Portugal.|Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Universidade do Porto, Porto, Portugal.
authors.forename: H
authors.initials: H
authors.lastname: Bousbaa
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D059566:M Phase Cell Cycle Checkpoints / Q000235:genetics; D064246:Mad2 Proteins / Q000032:analysis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D015996:Survival Rate
chemical_list: C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D012333:RNA, Messenger; C584277:BUB1 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: BubR1; Mad2; oral cancer; prognosis; proliferation; spindle assembly checkpoint