title: Role of Akt in growth and survival of PANC-1 pancreatic cancer cells.
abstract: BACKGROUND
  Akt is involved in different cellular processes such as cell growth, cell differentiation, and anti-apoptosis.
  
  
  OBJECTIVE
  To investigate the role of Akt in cell growth and survival in PANC-1 pancreatic cancer cells.
  
  
  RESULTS
  Insulin-like growth factor (IGF)-I induced Akt activation in a dose-dependent manner and stimulated anchorage-dependent and anchorage-independent cell growth of PANC-1 cells. In PANC-1 cells infected with adenovirus vectors carrying kinase-deficient Akt, anchorage-dependent and anchorage-independent cell growth was significantly reduced in the presence or absence of IGF-I compared with cells infected with adenovirus vectors carrying wild-type Akt, although IGF-I significantly stimulated cell growth in both transfected cell lines. Conversely, in PANC-1 cells infected with adenovirus vectors carrying kinase-deficient Akt, typical DNA laddering was undetectable in DNA fragmentation assay, and DNA 3;-OH reactivity was not detected in TUNEL assay. We then examined the role of phosphatidylinositol 3-kinase (PI3-K), an upstream mediator of Akt, on cell survival. In PANC-1 cells infected with adenovirus vector carrying a deletion mutant of the 85-kDa regulatory subunit of PI3-K and in cells treated with PI3-K inhibitor wortmannin, typical DNA laddering was evident in DNA fragmentation assay. In TUNEL assay, nuclear condensation and DNA 3;-OH reactivity was observed in approximately 30% of these cells.
  
  
  CONCLUSIONS
  The present results indicate that Akt is implicated in cell growth, but not in survival in PANC-1 cells. These results suggest that there may be an alternative survival signal cascade from PI3-K in PANC-1 cells.
authors.affiliation: Second Department of Internal Medicine, Kobe University School of Medicine, Kobe 650-0017, Japan.
authors.forename: Zan
authors.initials: Z
authors.lastname: Yao
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Okabayashi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yutsudo
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Kitamura
authors.forename: Wataru
authors.initials: W
authors.lastname: Ogawa
authors.forename: Masato
authors.initials: M
authors.lastname: Kasuga
mesh_terms: D017209:Apoptosis; D002455:Cell Division; D004789:Enzyme Activation; D005822:Genetic Vectors; D006801:Humans; D007334:Insulin-Like Growth Factor I; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D014407:Tumor Cells, Cultured
chemical_list: D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C494918:AKT1 protein, human