title: Subcellular localization of EGFR in esophageal carcinoma cell lines.
abstract: BACKGROUND
  The EGF receptor is a therapeutic target in cancer cells, whereby mutations of EGFR and/or signalling members act as predictive markers. EGFR however also exhibits dynamic changes of subcellular localization, leading to STAT5 complex formation, nuclear translocation and induction of Aurora-A expression in squamous cancer cells. We previously described high EGFR and Aurora-A expression in esophageal cancer cells. Here, we investigated subcellular localization of EGFR and STAT5 in esophageal cancer cells.
  
  
  RESULTS
  Quantitative immunofluorescence analyses of four esophageal cancer cell lines reflecting esophageal squamous cell carcinomas (ESCC) and esophageal adenocarcinomas (EAC) revealed that the subcellular localization of EGFR was shifted from a membranous to cytoplasmic localization upon EGF-stimulation in OE21 (ESCC) cells. Thereby, EGFR in part co-localized with E-Cadherin. In parallel, phosphorylated STAT5-Tyr694 appeared to increase in the nucleus and to decrease at the cell membrane. In three additional cell lines, EGFR was only marginally (Kyse-410/ESCC; OE19/EAC) and weakly (OE33, EAC) detectable at the cell membrane. Partial co-localization of EGFR and E-Cadherin occurred in OE33 cells. Post EGF-stimulation, EGFR was detected in the cytoplasm, resembling endosomal compartments. Furthermore, OE19 and OE33 exhibited nuclear STAT5-Tyr694 phosphorylation upon EGF-stimulation. None of the four cell lines showed nuclear EGFR expression and localization.
  
  
  CONCLUSIONS
  In contrast to other (squamous) cancer cells, activation of EGFR in esophageal squamous cancer cells does not result in nuclear translocation of EGFR. Still, the subcellular localization of EGFR may influence STAT5-associated signaling pathways in esophageal cancer cells and hence possibly also the responses to ErbB, respective EGFR-targeted therapies.
authors.affiliation: Institute of Surgical Pathology, Department of Pathology, University Medical Center, Breisacherstrasse 115A, 79106, Freiburg, Germany.
authors.forename: Lucas
authors.initials: L
authors.lastname: Spohn
authors.affiliation: Institute of Surgical Pathology, Department of Pathology, University Medical Center, Breisacherstrasse 115A, 79106, Freiburg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Fichter
authors.affiliation: Institute of Surgical Pathology, Department of Pathology, University Medical Center, Breisacherstrasse 115A, 79106, Freiburg, Germany.|German Consortium for Translational Cancer Research (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Werner
authors.affiliation: Institute of Surgical Pathology, Department of Pathology, University Medical Center, Breisacherstrasse 115A, 79106, Freiburg, Germany. silke.lassmann@uniklinik-freiburg.de.|German Consortium for Translational Cancer Research (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany. silke.lassmann@uniklinik-freiburg.de.|BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany. silke.lassmann@uniklinik-freiburg.de.
authors.forename: Silke
authors.initials: S
authors.lastname: Lassmann
keywords: EGFR; Esophageal cancer cells; STAT5; Subcellular localization