title: PTEN loss-mediated Akt activation increases the properties of cancer stem-like cell populations in prostate cancer.
abstract: OBJECTIVE
  To demonstrate that the PTEN/PI3K/Akt/NF-κB pathway plays an important role in regulating the prostate cancer stem-like cell population by upregulating ABCG2.
  
  
  METHODS
  Targeted PTEN knockdown in human prostate DU145 and 22Rv1 cells using a small interfering RNA were confirmed by immunoblot analysis using antibodies of PTEN, phospho-Akt, Akt, and α-tubulin. Knockdown PTEN DU145 and 22Rv1 cells were augmented, and the stem cell-like properties were examined by cell viability and tumor sphere formation and treated by Akt IV inhibitor to provide the signal transduction pathway. Luciferase activity assays were performed.
  
  
  RESULTS
  The knockdown of PTEN in prostate cancer cell lines increased the stem-like properties of the cells, including their sphere-forming ability, stem cell population number, epithelial-mesenchymal transition-related gene expression, and ABCG2 expression. Additionally, PTEN expression was highly associated with elevated expression of phospho-Akt. Treatment with an Akt inhibitor suppressed the PTEN-mediated effects on the properties of these stem-like cells as well as drug resistance, ABCG2 expression, and the NF-κB pathway.
  
  
  CONCLUSIONS
  The loss of PTEN in prostate cancer cells resulted in an increased PI3K/Akt pathway. Due to the Akt activation, PTEN loss may play an important role in prostate cancer by promoting cancer stemness through a mechanism that involves enhanced NF-κB signaling.
authors.affiliation: Laboratory of Cell Regulation and Carcinogenesis, CHA Cancer Institute, CHA University, Seoul, Korea.
authors.forename: Ran-Ju
authors.initials: RJ
authors.lastname: Kim
authors.forename: Eunjin
authors.initials: E
authors.lastname: Bae
authors.forename: Young Kwon
authors.initials: YK
authors.lastname: Hong
authors.forename: Jae Yup
authors.initials: JY
authors.lastname: Hong
authors.forename: Nam Keun
authors.initials: NK
authors.lastname: Kim
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Ahn
authors.forename: Jong Jin
authors.initials: JJ
authors.lastname: Oh
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Park
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D016328:NF-kappa B; D009363:Neoplasm Proteins; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human