title: Integrin-linked kinase regulates phosphatase and tensin homologue activity to promote tumorigenesis in neuroblastoma cells.
abstract: BACKGROUND
  The phosphatidylinositol 3-kinase (PI3K), a critical intracellular pathway, is negatively regulated by phosphatase and tensin homologue (PTEN). Integrin-linked kinase (ILK) induces phosphorylation of Akt leading to an increase in cell survival. However, a potential interaction between ILK and PTEN activity in neuroblastoma cells is unknown. We sought to examine the relationship between ILK and PTEN in the PI3K/Akt signaling pathway in neuroblastoma tumorigenesis.
  
  
  METHODS
  The human neuroblastoma cell line, BE(2)-C, was transfected with small interfering or short hairpin RNA to silence ILK expression. A plasmid containing the ILK wild-type (ILK wt) gene was transfected to overexpress ILK. Cell proliferation was assessed, and anchorage independence was measured by soft agar assay. Insulin-like growth factor-1 was used to stimulate the PI3K/Akt pathway. Protein levels were determined by Western blotting.
  
  
  RESULTS
  Transient silencing of ILK produced correlative decreases in PTEN expression, cell proliferation, and soft agar colony formation. Conversely, stably transfected ILK knockdown cells showed an increase in phospho-Akt levels, leading to cell proliferation.
  
  
  CONCLUSIONS
  ILK plays an important role in the regulation of PI3K/Akt pathway via PTEN or an upstream effector of PTEN. The effects of ILK silencing on PTEN expression seem to be critically dependent on duration of ILK dysregulation.
authors: Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors: Chase J
authors: CJ
authors: Taylor
authors: Jingbo
authors: J
authors: Qiao
authors: Nadja C
authors: NC
authors: Colon
authors: Cameron
authors: C
authors: Schlegel
authors: Erlena
authors: E
authors: Josifi
authors: Dai H
authors: DH
authors: Chung
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism / Q000503:physiopathology*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D000099200:Scaffold Protein ILK
chemical_list: D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK; C494929:PTEN protein, human