title: N-myc downstream regulated gene-1 expression correlates with reduced pancreatic cancer growth and increased apoptosis in vitro and in vivo.
abstract: BACKGROUND
  The role of N-myc downstream regulated gene-1 (NDRG1) in cancer has recently gained interest, as potential regulator of cell death and tumor suppressor. Although its normal function in the pancreas is largely unknown, loss of NDRG1 expression is associated with a more aggressive tumor phenotype and poor outcome in pancreatic cancer patients.
  
  
  METHODS
  NDRG1 expression was determined in human pancreatic cancer samples and across a panel of 6 pancreatic cancer cell lines. HPAF-II cells were stably transfected with full-length NDRG1 (HP(NDRG1)) or the empty vector (HP(NEG)). BxPC-3 cells were silenced for NDRG1. These cells were analyzed for cell growth, cell cycle, apoptosis, and pro-apoptotic gene expression. They were transduced with lentiviral vector expressing luciferase to establish an orthotopic xenograft model. In vivo tumor growth was assessed by bioluminescence imaging.
  
  
  RESULTS
  Growth of HP(NDRG1) was impaired in anchorage-dependent and abolished in anchorage-independent assays respectively. These results were confirmed in BxPC-3 silenced for NDRG1. Growth inhibition was induced by enhanced apoptosis. Seven pro-apoptotic genes were up-regulated in HP(NDRG1) cells. In vivo, HP(NDRG1) tumors showed no growth over 6 weeks, while HP(NEG) tumors grew prominently, correlating with a 325-fold increase in light emission.
  
  
  CONCLUSIONS
  In this model we found that expression of NDRG1 correlates with decreased growth in human pancreatic cancer cells in vitro and in vivo. The observation that NDRG1 completely inhibited growth in anchorage-independent assays and in vivo supports a biological function as a tumor suppressor in pancreatic cancer.
authors.affiliation: Hirshberg Laboratories for Pancreatic Cancer Research, Department of Surgery, UCLA Center for Excellence in Pancreatic Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Eliane
authors.initials: E
authors.lastname: Angst
authors.forename: David W
authors.initials: DW
authors.lastname: Dawson
authors.forename: Deborah
authors.initials: D
authors.lastname: Stroka
authors.forename: Beat
authors.initials: B
authors.lastname: Gloor
authors.forename: Jenny
authors.initials: J
authors.lastname: Park
authors.forename: Daniel
authors.initials: D
authors.lastname: Candinas
authors.forename: Howard A
authors.initials: HA
authors.lastname: Reber
authors.forename: O Joe
authors.initials: OJ
authors.lastname: Hines
authors.forename: Guido
authors.initials: G
authors.lastname: Eibl
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D020868:Gene Silencing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D014183:Transplantation, Heterologous; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein