title: FOXM1 and polo-like kinase 1 are co-ordinately overexpressed in patients with gastric adenocarcinomas.
abstract: BACKGROUND
  Gastric cancers present late in life with advanced disease and carry a poor prognosis. Polo-like Kinase 1 (PLK1) is a mitotic kinase with regulatory functions during G2/M and mitosis in the cell cycle. In mammalian cells, there is an intricate co-regulatory relationship between PLK1 and the forkhead transcription factor FOXM1. It has been demonstrated that individually either PLK1 or FOXM1 expression predicts poorer survival. However, the co-expression of both of these markers in gastric adenocarcinomas has not been reported previously.
  
  
  METHODS
  We aimed to assess the expression of PLK1 and FOXM1 in Gastric adenocarcinomas in a Western Population, to examine whether there is a relationship of PLK1 to FOXM1 in cancer samples. We assess both the protein and mRNA expression in this patient population by Tissue Microarray immunohistochemistry and RT-PCR.
  
  
  RESULTS
  Immunohistochemistry was performed on biopsy samples from 79 patients with gastric cancer. Paired normal controls were available in 47 patients. FOXM1 expression was significantly associated with gastric adenocarcinoma (p = 0.001). PLK1 and FOXM1 co-expression was demonstrated in 6/8 (75 %) tumours when analysed by RT-PCR. FOXM1 is overexpressed in a large proportion of gastric carcinomas at the protein level and FOXM1 and PLK1 are concomitantly overexpressed at the mRNA level in this cancer type.
  
  
  CONCLUSIONS
  This study has demonstrated that FOXM1 and its target gene PLK1 are coordinately overexpressed in a proportion of gastric adenocarcinomas. This suggests that chemotherapeutic treatments that target this pathway may be of clinical utility.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK. martyn.dibb@nhs.net.|Faculty of Medical and Human Sciences, University of Manchester, Oxford Road, Manchester, UK. martyn.dibb@nhs.net.
authors.forename: M
authors.initials: M
authors.lastname: Dibb
authors.affiliation: Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK. namshik.han@gmail.com.
authors.forename: N
authors.initials: N
authors.lastname: Han
authors.affiliation: Department of Histopathology, Salford Royal Foundation Trust, Stott Lane, Salford, M6 8HD, UK. jamil.choudhury@srft.nhs.uk.
authors.forename: J
authors.initials: J
authors.lastname: Choudhury
authors.affiliation: Faculty of Medical and Human Sciences, University of Manchester, Oxford Road, Manchester, UK. Stephen.hayes@srft.nhs.uk.|Department of Histopathology, Salford Royal Foundation Trust, Stott Lane, Salford, M6 8HD, UK. Stephen.hayes@srft.nhs.uk.
authors.forename: S
authors.initials: S
authors.lastname: Hayes
authors.affiliation: School of Cancer and Enabling Sciences, Christie Hospital, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK. Helen.valentine@manchester.ac.uk.
authors.forename: H
authors.initials: H
authors.lastname: Valentine
authors.affiliation: School of Cancer and Enabling Sciences, Christie Hospital, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK. Catharine.west@manchester.ac.uk.
authors.forename: C
authors.initials: C
authors.lastname: West
authors.affiliation: Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK. Andrew.d.sharrocks@manchester.ac.uk.
authors.forename: A D
authors.initials: AD
authors.lastname: Sharrocks
authors.affiliation: Faculty of Medical and Human Sciences, University of Manchester, Oxford Road, Manchester, UK. yeng.ang@srft.nhs.uk.|GI Science Centre, Salford Royal NHS FT, University of Manchester, Stott Lane, Salford, M6 8HD, UK. yeng.ang@srft.nhs.uk.
authors.forename: Yeng S
authors.initials: YS
authors.lastname: Ang
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D013274:Stomach Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; 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; D012333:RNA, Messenger; D000097869:Polo-Like Kinase 1; C107585:FOXM1 protein, human