title: Impaired expression of protein phosphatase 2A subunits enhances metastatic potential of human prostate cancer cells through activation of AKT pathway.
abstract: BACKGROUND
  Protein phosphatase 2A (PP2A) is a dephosphorylating enzyme, loss of which can contribute to prostate cancer (PCa) pathogenesis. The aim of this study was to analyse the transcriptional and translational expression patterns of individual subunits of the PP2A holoenzyme during PCa progression.
  
  
  METHODS
  Immunohistochemistry (IHC), western blot, and real-time PCR was performed on androgen-dependent (AD) and androgen-independent (AI) PCa cells, and benign and malignant prostate tissues for all the three PP2A (scaffold, regulatory, and catalytic) subunits. Mechanistic and functional studies were performed using various biochemical and cellular techniques.
  
  
  RESULTS
  Through immunohistochemical analysis we observed significantly reduced levels of PP2A-A and -B'γ subunits (P<0.001 and P=0.0002) in PCa specimens compared with benign prostate. Contemporarily, there was no significant difference in PP2A-C subunit expression between benign and malignant tissues. Similar to the expression pattern observed in tissues, the endogenous levels of PP2A-A and B'γ subunits were abrogated from the low metastatic to high metastatic and AD to AI cell line models, without any change in the catalytic subunit expression. Furthermore, using in vitro studies we demonstrated that PP2A-Aα scaffold subunit has a role in dampening AKT, β-catenin, and FAK (focal adhesion kinase) signalling.
  
  
  CONCLUSIONS
  We conclude that loss of expression of scaffold and regulatory subunits of PP2A is responsible for its altered function during PCa pathogenesis.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA.
authors.forename: P
authors.initials: P
authors.lastname: Pandey
authors.forename: P
authors.initials: P
authors.lastname: Seshacharyulu
authors.forename: S
authors.initials: S
authors.lastname: Das
authors.forename: S
authors.initials: S
authors.lastname: Rachagani
authors.forename: M P
authors.initials: MP
authors.lastname: Ponnusamy
authors.forename: Y
authors.initials: Y
authors.lastname: Yan
authors.forename: S L
authors.initials: SL
authors.lastname: Johansson
authors.forename: K
authors.initials: K
authors.lastname: Datta
authors.forename: M
authors.initials: M
authors.lastname: Fong Lin
authors.forename: S K
authors.initials: SK
authors.lastname: Batra
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D015536:Down-Regulation / Q000502:physiology; D004789:Enzyme Activation / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008297:Male; D008954:Models, Biological; D009362:Neoplasm Metastasis; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D054648:Protein Phosphatase 2 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D021122:Protein Subunits; D051058:Oncogene Protein v-akt; C517189:PPP2CA protein, human; D054648:Protein Phosphatase 2