title: Expression of NRG1 and its receptors in human bladder cancer.
abstract: BACKGROUND
  Therapies targeting ERBB2 have shown success in the clinic. However, response is not determined solely by expression of ERBB2. Levels of ERBB3, its preferred heterodimerisation partner and ERBB ligands may also have a role.
  
  
  METHODS
  We measured NRG1 expression by real-time quantitative RT-PCR and ERBB receptors by western blotting and immunohistochemistry in bladder tumours and cell lines.
  
  
  RESULTS
  NRG1α and NRG1β showed significant coordinate expression. NRG1β was upregulated in 78% of cell lines. In tumours, there was a greater range of expression with a trend towards increased NRG1α with higher stage and grade. Increased expression of ERBB proteins was detected in 15% (EGFR), 20% (ERBB2), 41% (ERBB3) and 0% (ERBB4) of cell lines. High EGFR expression was detected in 28% of tumours, associated with grade and stage (P=0.05; P=0.04). Moderate or high expression of ERBB2 was detected in 22% and was associated with stage (P=0.025). Cytoplasmic ERBB3 was associated with high tumour grade (P=0.01) and with ERBB2 positivity. In cell lines, NRG1β expression was significantly inversely related to ERBB3, but this was not confirmed in tumours.
  
  
  CONCLUSIONS
  There is a wide spectrum of NRG1 and ERBB receptor expression in bladder cancer. In advanced tumours, EGFR, ERBB2 and ERBB3 upregulation is common and there is a relationship between expression of ERBB2 and ERBB3 but not the NRG1 ligand.
authors.affiliation: Cancer Research UK Clinical Centre, St James University Hospital, Beckett Street, Leeds LS9 7TF, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Forster
authors.forename: A B
authors.initials: AB
authors.lastname: Paul
authors.forename: P
authors.initials: P
authors.lastname: Harnden
authors.forename: M A
authors.initials: MA
authors.lastname: Knowles
mesh_terms: D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000032:analysis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D020890:Neuregulin-1 / Q000032:analysis* / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D020893:Receptor, ErbB-3 / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000473:pathology
chemical_list: D066246:ErbB Receptors; D020890:Neuregulin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C094131:NRG1 protein, human; C508053:ERBB2 protein, human