Anti-ERBB2 sh-RNA suppress both cell growth and tumor growth in ERBB2-overexpressing upper gastrointestinal adenocarcinomas.
BACKGROUND
ERBB2 is overexpressed in 15-25% of upper gastrointestinal adenocarcinomas. We use a stable lentiviral shRNA model to demonstrate that ERBB2 suppression in upper gastrointestinal adenocarcinomas with documented ERBB2 amplification effectively decreases ERBB2 protein levels and decreases cell viability. Further, we evaluate tumor growth of cells treated with the ERBB2 shRNA.


METHODS
Three upper gastrointestinal adenocarcinoma cells lines with varying ERBB2 levels were treated with one of three separate lentiviral green fluorescent protein (GFP)-labeled ERBB2 shRNA vectors or a nonsilencing control shRNA vector for 6 h. Protein levels on day 6 and cell viability was evaluated on days 3-10. A xenograft in vivo experiment was performed using OE19 cells pretransduced with ERBB2 shRNA to evaluate tumor growth.


RESULTS
ERBB2 protein levels decreased by 80%. ERBB2 knockdown significantly decreased cell viability in cell lines with high ERBB2 levels. In vivo tumor growth was suppressed in ERBB2-shRNA-treated groups.


CONCLUSIONS
ERBB2 suppression based on a stable lentiviral shRNA transfection system effectively decreases cell viability in cell lines with amplification of ERBB2 as compared to cell lines without overexpression. ERBB2 knockdown significantly decreases tumor growth in vivo. ERBB2-directed therapy may be of benefit in the subset of patients with gastrointestinal adenocarcinomas exhibiting overamplification of ERBB2.
Arrington
Amanda K
AK
Department of Surgery, University of Minnesota, 420 Delaware St SE, MMC195, Minneapolis, MN 55455, USA.
Davydova
Julia
J
Vickers
Selwyn M
SM
Yamamoto
Masato
M
D000230:Adenocarcinoma / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D051379:Mice; D016372:RNA, Antisense / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000235:genetics*; D041742:Upper Gastrointestinal Tract; D023041:Xenograft Model Antitumor Assays
D016372:RNA, Antisense; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human