title: The FOXM1-PLK1 axis is commonly upregulated in oesophageal adenocarcinoma.
abstract: BACKGROUND
  The transcription factor FOXM1 is an important regulator of the cell cycle through controlling periodic gene expression during the G2 and M phases. One key target for FOXM1 is the gene encoding the protein kinase PLK1 and PLK1 itself acts in a positive feedback loop to phosphorylate and activate FOXM1. Both FOXM1 and PLK1 have been shown to be overexpressed in a variety of different tumour types.
  
  
  METHODS
  We have used a combination of RT-PCR, western blotting, tissue microarrays and metadata analysis of microarray data to study whether the FOXM1-PLK1 regulatory axis is upregulated and operational in oesophageal adenocarcinoma.
  
  
  RESULTS
  FOXM1 and PLK1 are expressed in oesophageal adenocarcinoma-derived cell lines and demonstrate cross-regulatory interactions. Importantly, we also demonstrate the concomitant overexpression of FOXM1 and PLK1 in a large proportion of oesophageal adenocarcinoma samples. This co-association was extended to the additional FOXM1 target genes CCNB1, AURKB and CKS1. In a cohort of patients who subsequently underwent surgery, the expression of several FOXM1 target genes was prognostic for overall survival.
  
  
  CONCLUSIONS
  FOXM1 and its target gene PLK1 are commonly overexpressed in oesophageal adenocarcinomas and this association can be extended to other FOXM1 target genes, providing potentially important biomarkers for predicting post-surgery disease survival.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
authors.forename: M
authors.initials: M
authors.lastname: Dibb
authors.forename: N
authors.initials: N
authors.lastname: Han
authors.forename: J
authors.initials: J
authors.lastname: Choudhury
authors.forename: S
authors.initials: S
authors.lastname: Hayes
authors.forename: H
authors.initials: H
authors.lastname: Valentine
authors.forename: C
authors.initials: C
authors.lastname: West
authors.forename: Y S
authors.initials: YS
authors.lastname: Ang
authors.forename: A D
authors.initials: AD
authors.lastname: Sharrocks
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015331:Cohort Studies; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C107585:FOXM1 protein, human