title: ERBB2 suppression decreases cell growth via apoptosis in gastrointestinal adenocarcinomas.
abstract: BACKGROUND
  Although the incidence of adenocarcinoma of the esophageal and gastroesophageal junction has increased at an alarming rate in the past 30 years, little improvement has been made in treatment strategies. Previous studies have demonstrated that many upper gastrointestinal (GI) adenocarcinomas exhibit ERBB2 amplification. In cancers proven to have similar amplification, such as breast, ERBB2-targeted therapies have dramatically improved overall survival and disease-free rates of survival. This study uses siRNA to knockdown ERBB2 in GI adenocarcinoma cell lines to evaluate cell viability, apoptosis, and changes in cell cycle.
  
  
  METHODS
  A cell line with a baseline amount of ERBB2 (Seg-1) and 2 upper GI adenocarcinoma cell lines with known amplification of ERBB2 (esophageal [OE19] and gastric [MKN45]) were treated with 120 pmol of 1 of 2 independent ERBB2 siRNAs or control siRNA for 6 hours.
  
  
  RESULTS
  We demonstrate that knockdown of ERBB2 in esophageal and gastric cancer cell lines with known ERBB2 amplification effectively decreases ERBB2 protein levels and decreases cell viability mainly via apoptotic pathways.
  
  
  CONCLUSIONS
  ERBB-directed therapy may be of benefit in the subset of patients with GI adenocarcinomas exhibiting amplification of ERBB2.
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Arrington
authors.forename: Peter S
authors.initials: PS
authors.lastname: Dahlberg
authors.forename: Julia
authors.initials: J
authors.lastname: Davydova
authors.forename: Selwyn M
authors.initials: SM
authors.lastname: Vickers
authors.forename: Masato
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002470:Cell Survival; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004943:Esophagogastric Junction; D005784:Gene Amplification; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases