title: The ERK MAP kinase-PEA3/ETV4-MMP-1 axis is operative in oesophageal adenocarcinoma.
abstract: BACKGROUND
  Many members of the ETS-domain transcription factor family are important drivers of tumourigenesis. In this context, their activation by Ras-ERK pathway signaling is particularly relevant to the tumourigenic properties of many ETS-domain transcription factors. The PEA3 subfamily of ETS-domain transcription factors have been implicated in tumour metastasis in several different cancers.
  
  
  RESULTS
  Here, we have studied the expression of the PEA3 subfamily members PEA3/ETV4 and ER81/ETV1 in oesophageal adenocarcinomas and determined their role in oesophageal adenocarcinoma cell function. PEA3 plays an important role in controlling both the proliferation and invasive properties of OE33 oesophageal adenocarcinoma cells. A key target gene is MMP-1. The ERK MAP kinase pathway activates PEA3 subfamily members and also plays a role in these PEA3 controlled events, establishing the ERK-PEA3-MMP-1 axis as important in OE33 cells. PEA3 subfamily members are upregulated in human adenocarcinomas and expression correlates with MMP-1 expression and late stage metastatic disease. Enhanced ERK signaling is also more prevalent in late stage oesophageal adenocarcinomas.
  
  
  CONCLUSIONS
  This study shows that the ERK-PEA3-MMP-1 axis is upregulated in oesophageal adenocarcinoma cells and is a potentially important driver of the metastatic progression of oesophageal adenocarcinomas.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Keld
authors.forename: Baoqiang
authors.initials: B
authors.lastname: Guo
authors.forename: Paul
authors.initials: P
authors.lastname: Downey
authors.forename: Christian
authors.initials: C
authors.lastname: Gulmann
authors.forename: Yeng S
authors.initials: YS
authors.lastname: Ang
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Sharrocks
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D017500:Adenovirus E1A Proteins; C079853:ETV4 protein, human; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; C065788:transcription factor PEA3; D048049:Extracellular Signal-Regulated MAP Kinases; D020781:Matrix Metalloproteinase 1