Expression of Akt kinase-interacting protein 1, a scaffold protein of the PI3K/PDK1/Akt pathway, in pancreatic cancer

Pancreas. 2014 Oct;43(7):1093-100. doi: 10.1097/MPA.0000000000000168.

Abstract

Objectives: 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.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adenocarcinoma, Papillary / genetics
  • Adenocarcinoma, Papillary / metabolism
  • Adenocarcinoma, Papillary / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Adenosquamous / genetics
  • Carcinoma, Adenosquamous / metabolism
  • Carcinoma, Adenosquamous / pathology
  • Cell Division
  • Cell Line, Tumor
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Phosphatidylinositol 3-Kinases / physiology
  • Protein Serine-Threonine Kinases / physiology
  • Proto-Oncogene Proteins c-akt / physiology
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • RNA Interference
  • RNA, Small Interfering / pharmacology
  • Signal Transduction

Substances

  • CC2D1A protein, human
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • PDK1 protein, human
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • RNA, Small Interfering
  • AKT1 protein, human
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt