title: Expression of Akt kinase-interacting protein 1, a scaffold protein of the PI3K/PDK1/Akt pathway, in pancreatic cancer.
abstract: OBJECTIVE
  Akt kinase-interacting protein 1 (Aki1) has been reported to be a scaffold protein of the PI3K (phosphoinositide 3-kinase)/PDK1 (3-phosphoinositide-dependent protein kinase)/Akt pathway and to interact with epidermal growth factor receptor signaling. Although Aki1 has been reported to be expressed in lung cancer, the significance of its expression in pancreatic cancer has not been clarified.
  
  
  METHODS
  The expression of Aki1 and its associated proteins was assayed in pancreatic cancer cell lines, and its involvement in cell viability was examined by treatment with Aki1 small interfering RNA. We also assessed the immunohistochemical expression of Aki1 in tissue samples from 60 patients with pancreatic cancer.
  
  
  RESULTS
  All of the pancreatic cancer cell lines expressed Aki1 and its associated proteins at various levels. Treatment with Aki1 small interfering RNA or PI3K inhibitor inhibited the viability of Panc1 cells. Silencing of Aki1 in Panc1 cells reduced the phosphorylation of Akt and increased the phosphorylation of cleaved PARP. The Aki1 was expressed in 25 (42%) of the 60 pancreatic cancers, but there was no correlation between Aki1 expression and clinicopathologic parameters. We observed a statistically significant correlation between Aki1 and p-Akt expression (P = 0.016).
  
  
  CONCLUSIONS
  Inhibition of the Aki1-Akt axis may be a therapeutic target in some patients with pancreatic cancer.
authors.affiliation: From the *Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan; †Division of Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan; and ‡Department of Gastroenterological Surgery and §Division of Pathology, Kanazawa University, Kanazawa, Japan.
authors.forename: Koushiro
authors.initials: K
authors.lastname: Ohtsubo
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Yamada
authors.forename: Lu
authors.initials: L
authors.lastname: Zhao
authors.forename: Tie-Feng
authors.initials: TF
authors.lastname: Jin
authors.forename: Shinji
authors.initials: S
authors.lastname: Takeuchi
authors.forename: Hisatsugu
authors.initials: H
authors.lastname: Mouri
authors.forename: Kaname
authors.initials: K
authors.lastname: Yamashita
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yasumoto
authors.forename: Naoya
authors.initials: N
authors.lastname: Fujita
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohta
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ikeda
authors.forename: Seiji
authors.initials: S
authors.lastname: Yano
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000231:Adenocarcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018196:Carcinoma, Adenosquamous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D034741:RNA, Small Interfering; C512283:CC2D1A protein, human; C000631429:PDK1 protein, human; C494918:AKT1 protein, human