title: The silencing of N-myc downstream-regulated gene-1 in an orthotopic pancreatic cancer model leads to more aggressive tumor growth and metastases.
abstract: BACKGROUND
  The understanding of molecular mechanisms leading to poor prognosis in pancreatic cancer may help develop treatment options. N-myc downstream-regulated gene-1 (NDRG1) has been correlated to better prognosis in pancreatic cancer. Therefore, we thought to analyze how the loss of NDRG1 affects progression in an orthotopic xenograft animal model of recurrence.
  
  
  METHODS
  Capan-1 cells were silenced for NDRG1 (C(sil)) or transfected with scrambled shRNA (C(scr)) and compared for anchorage-dependent and anchorage-independent growth, invasion and tube formation in vitro. In an orthotopic xenograft model of recurrence tumors were grown in the pancreatic tail. The effect of NDRG1 silencing was evaluated on tumor size and metastasis.
  
  
  RESULTS
  The silencing of NDRG1 in Capan-1 cells leads to more aggressive tumor growth and metastasis. We found faster cell growth, double count of invaded cells and 1.8-fold increase in tube formation in vitro. In vivo local tumors were 5.9-fold larger (p = 0.006) and the number of metastases was higher in animals with tumors silenced for NDRG1 primarily (3 vs. 1.1; p = 0.005) and at recurrence (3.3 vs. 0.9; p = 0.015).
  
  
  CONCLUSIONS
  NDRG1 may be an interesting therapeutic target as its silencing in human pancreatic cancer cells leads to a phenotype with more aggressive tumor growth and metastasis.
authors: Department of Visceral Surgery and Medicine, Inselspital University of Bern, Bern, Switzerland.
authors: Corina
authors: C
authors: Kim-Fuchs
authors: Sebastian
authors: S
authors: Winterhalder
authors: Annja
authors: A
authors: Winter
authors: Thomas
authors: T
authors: Malinka
authors: Diana
authors: D
authors: Born
authors: Stephan
authors: S
authors: Schäfer
authors: Deborah
authors: D
authors: Stroka
authors: Beat
authors: B
authors: Gloor
authors: Daniel
authors: D
authors: Candinas
authors: Eliane
authors: E
authors: Angst
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D020868:Gene Silencing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics*; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein