title: HER3 is a determinant for poor prognosis in melanoma.
abstract: OBJECTIVE
  The epidermal growth factor receptor family member HER3 is overexpressed in diverse human cancers and has been associated with poor prognosis in breast, lung, and ovarian cancer. However, the relevance of HER3 with regard to its prognostic significance and function in primary melanoma and metastases remains largely elusive.
  
  
  METHODS
  HER3 protein expression was analyzed immunohistochemically using tissue microarrays of 130 primary melanoma and 87 metastases relative to established clinical variables. The possibility of an influence of HER3 on melanoma cell proliferation, migration, invasion, and chemotherapy-induced apoptosis was studied in human melanoma cell lines.
  
  
  RESULTS
  We show that HER3 is frequently expressed in malignant melanoma and metastases at elevated levels. High HER3 expression may serve as a prognostic marker because it correlates with cell proliferation, tumor progression, and reduced patient survival. Suppression of HER3 expression by RNA interference reduces melanoma cell proliferation, migration, and invasion in vitro. In addition, down-regulation of HER3 synergistically enhances dacarbazine-induced apoptosis. Moreover, monoclonal antibodies specific for the extracellular portion of HER3 efficiently block heregulin-induced proliferation, migration, and invasion of melanoma cell lines.
  
  
  CONCLUSIONS
  Our results provide novel insights into the role of HER3 in melanoma and point out new possibilities for therapeutic intervention.
authors.affiliation: Department of Molecular Biology, Max-Planck Institute of Biochemistry, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Reschke
authors.forename: Daniela
authors.initials: D
authors.lastname: Mihic-Probst
authors.forename: Edward Htun
authors.initials: EH
authors.lastname: van der Horst
authors.forename: Pjotr
authors.initials: P
authors.lastname: Knyazev
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wild
authors.forename: Markus
authors.initials: M
authors.lastname: Hutterer
authors.forename: Stefanie
authors.initials: S
authors.lastname: Meyer
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.forename: Axel
authors.initials: A
authors.lastname: Ullrich
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D011379:Prognosis; D034622:RNA Interference; D020893:Receptor, ErbB-3 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D020893:Receptor, ErbB-3