title: Farnesoid X receptor, overexpressed in pancreatic cancer with lymph node metastasis promotes cell migration and invasion.
abstract: BACKGROUND
  Lymph node metastasis is one of the most important adverse prognostic factors for pancreatic cancer. The aim of this study was to identify novel lymphatic metastasis-associated markers and therapeutic targets for pancreatic cancer.
  
  
  METHODS
  DNA microarray study was carried out to identify genes differentially expressed between 17 pancreatic cancer tissues with lymph node metastasis and 17 pancreatic cancer tissues without lymph node metastasis. The microarray results were validated by real-time PCR. Immunohistochemistry and western blotting were used to examine the expression of farnesoid X receptor (FXR). The function of FXR was studied by small interfering RNA and treatment with FXR antagonist guggulsterone and FXR agonist GW4064.
  
  
  RESULTS
  Farnesoid X receptor overexpression in pancreatic cancer tissues with lymph node metastasis is associated with poor patient survival. Small interfering RNA-mediated downregulation of FXR and guggulsterone-mediated FXR inhibition resulted in a marked reduction in cell migration and invasion. In addition, downregulation of FXR reduced NF-κB activation and conditioned medium from FXR siRNA-transfected cells showed reduced VEGF levels. Moreover, GW4064-mediated FXR activation increased cell migration and invasion.
  
  
  CONCLUSIONS
  These findings indicated that FXR overexpression plays an important role in lymphatic metastasis of pancreatic cancer and that downregulation of FXR is an effective approach for inhibition of pancreatic tumour progression.
authors.affiliation: Department of Health Science and Technology, Graduate School, SAIHST, Sungkyunkwan University, Seoul, Korea.
authors.forename: J Y
authors.initials: JY
authors.lastname: Lee
authors.forename: K T
authors.initials: KT
authors.lastname: Lee
authors.forename: J K
authors.initials: JK
authors.lastname: Lee
authors.forename: K H
authors.initials: KH
authors.lastname: Lee
authors.forename: K-T
authors.initials: KT
authors.lastname: Jang
authors.forename: J S
authors.initials: JS
authors.lastname: Heo
authors.forename: S H
authors.initials: SH
authors.lastname: Choi
authors.forename: Yil
authors.initials: Y
authors.lastname: Kim
authors.forename: J C
authors.initials: JC
authors.lastname: Rhee
mesh_terms: D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D004353:Drug Evaluation, Preclinical; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated