title: p8 inhibits the growth of human pancreatic cancer cells and its expression is induced through pathways involved in growth inhibition and repressed by factors promoting cell growth.
abstract: BACKGROUND
  p8 is a stress-induced protein with multiple functions and biochemically related to the architectural factor HMG-I/Y. We analyzed the expression and function of p8 in pancreatic cancer-derived cells.
  
  
  METHODS
  Expression of p8 was silenced in the human pancreatic cancer cell lines Panc-1 and BxPc-3 by infection with a retrovirus expressing p8 RNA in the antisense orientation. Cell growth was measured in control and p8-silenced cells. Influence on p8 expression of the induction of intracellular pathways promoting cellular growth or growth arrest was monitored.
  
  
  RESULTS
  p8-silenced cells grew more rapidly than control cells transfected with the empty retrovirus. Activation of the Ras-->Raf-->MEK-->ERK and JNK intracellular pathways down-regulated p8 expression. In addition, the MEK1/2 inhibitor U0126 and the JNK inhibitor SP600125 up-regulates expression of p8. Conversely, p38 or TGFbeta-1 induced p8 expression whereas the specific p38 inhibitor SB203580 down-regulated p8 expression. Finally, TGFbeta-1 induction was in part mediated through p38.
  
  
  CONCLUSIONS
  p8 inhibits the growth of human pancreatic cancer cells. p8 expression is induced through pathways involved in growth inhibition and repressed by factors that promote cell growth. These results suggest that p8 belongs to a pathway regulating the growth of pancreatic cancer cells.
authors: Centre de Recherche INSERM, EMI 0116, 163 Avenue de Luminy, Case 915, Parc Scientifique et Technologique de Luminy, 13288 Marseille Cedex, France. malicet@marseille.inserm.fr
authors: Cédric
authors: C
authors: Malicet
authors: Nathalie
authors: N
authors: Lesavre
authors: Sophie
authors: S
authors: Vasseur
authors: Juan L
authors: JL
authors: Iovanna
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D051792:Basic Helix-Loop-Helix Proteins; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D020868:Gene Silencing; D005822:Genetic Vectors / Q000235:genetics; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D016372:RNA, Antisense / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D018631:ras Proteins / Q000378:metabolism
chemical_list: D000873:Anthracenes; D051792:Basic Helix-Loop-Helix Proteins; D002070:Butadienes; D003470:Culture Media; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D007093:Imidazoles; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D009363:Neoplasm Proteins; D009570:Nitriles; D019908:Proto-Oncogene Proteins c-raf; D011725:Pyridines; D016372:RNA, Antisense; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D018631:ras Proteins; C491643:NUPR1 protein, human; C508960:TGFB1 protein, human; C113580:U 0126; C432165:pyrazolanthrone; C093642:SB 203580