title: αv integrin: a new gastrin target in human pancreatic cancer cells.
abstract: OBJECTIVE
  To analyse αv integrin expression induced by gastrin in pancreatic cancer models.
  
  
  METHODS
  αv integrin mRNA expression in human pancreatic cancer cells was analysed using a "cancer genes" array and confirmed by real-time reverse transcription-polymerase chain reaction (PCR). Western blotting and semi-quantitative immunohistochemistry were used to examine protein levels in human pancreatic cancer cell lines and pancreatic tissues, respectively. The role of αv integrin on gastrin-induced cell adhesion was examined using blocking anti-αv integrin monoclonal antibodies. Adherent cells were quantified by staining with crystal violet.
  
  
  RESULTS
  Using a "cancer genes" array we identified αv integrin as a new gastrin target gene in human pancreatic cancer cells. A quantitative real-time PCR approach was used to confirm αv integrin gene expression. We also demonstrate that Src family kinases and the PI 3-kinase, two signalling pathways specifically activated by the CCK-2 receptor (CCK2R), are involved in gastrin-mediated αv integrin expression. In contrast, inhibition of the ERK pathway was without any effect on αv integrin expression induced by gastrin. Our results also show that gastrin modulates cell adhesion via αv integrins. Indeed, in vitro adhesion assays performed on fibronectin show that gastrin significantly increases adhesion of pancreatic cancer cells. The use of blocking anti-αv integrin monoclonal antibodies completely reversed the increase in cell-substrate adhesion induced by gastrin. In addition, we showed in vivo that the targeted CCK2R expression in the pancreas of Elas-CCK2 mice, leads to the overexpression of αv integrin. This process may contribute to pancreatic tumour development observed in these transgenic animals.
  
  
  CONCLUSIONS
  αv integrin is a new gastrin target in pancreatic cancer models and contributes to gastrin effects on cell adhesion.
authors: INSERM UMR1037-Cancer Research Center of Toulouse, Paul Sabatier University Toulouse III, 31432 Toulouse Cedex 4, France.
authors: Celine
authors: C
authors: Cayrol
authors: Claudine
authors: C
authors: Bertrand
authors: Aline
authors: A
authors: Kowalski-Chauvel
authors: Laurence
authors: L
authors: Daulhac
authors: Elizabeth
authors: E
authors: Cohen-Jonathan-Moyal
authors: Audrey
authors: A
authors: Ferrand
authors: Catherine
authors: C
authors: Seva
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D005755:Gastrins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039564:Integrin alphaV / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D046228:Microarray Analysis / Q000379:methods; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D043887:Receptor, Cholecystokinin B / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D005755:Gastrins; D039564:Integrin alphaV; D043887:Receptor, Cholecystokinin B; D019869:Phosphatidylinositol 3-Kinases; D019061:src-Family Kinases