title: Expression of mTOR signaling pathway markers in prostate cancer progression.
abstract: BACKGROUND
  The PI3K/AKT/mTOR pathway is central to prostate cancer progression. A preliminary investigation of immuno-histochemical expression of mammalian target of rapamycin (mTOR) pathway markers was undertaken to identify patterns of expression in prostate tissue.
  
  
  METHODS
  Immunohistochemistry was performed on a custom-made prostate tissue array. Mean long scores and variability of long scores for each marker were recorded for normal lumenal cells, prostate intraepithelial neoplasia (PIN), and cancer.
  
  
  RESULTS
  Expression of PTEN decreased and mTOR signaling pathway markers increased in PIN and in cancer as compared to normal cells in the majority of samples. Overexpression of 4E-BP1 and p-4E-BP1 was observed in PIN and cancer. However, in cancer, the overexpression of 4E-BP1 was significantly higher than with any other marker.
  
  
  CONCLUSIONS
  Results suggest that 4E-BP1 overexpression is strongly associated with prostate cancer, especially when combined with PTEN and mTOR expression data. Hierarchical clustering analysis utilizing PTEN, mTOR, and 4E-BP1 separated normal from cancer cell populations in most cases.
authors.affiliation: Arizona Cancer Center, University of Arizona, 1525 N. Campbell Avenue, Tucson, AZ 85724, USA.
authors.forename: Celeste L
authors.initials: CL
authors.lastname: Kremer
authors.forename: Rob R
authors.initials: RR
authors.lastname: Klein
authors.forename: Jenny
authors.initials: J
authors.lastname: Mendelson
authors.forename: Walden
authors.initials: W
authors.lastname: Browne
authors.forename: Linda K
authors.initials: LK
authors.lastname: Samadzedeh
authors.forename: Kristie
authors.initials: K
authors.lastname: Vanpatten
authors.forename: Lindsey
authors.initials: L
authors.lastname: Highstrom
authors.forename: Gary A
authors.initials: GA
authors.lastname: Pestano
authors.forename: Raymond B
authors.initials: RB
authors.lastname: Nagle
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D018797:Cell Cycle Proteins; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000032:analysis*; D010750:Phosphoproteins / Q000032:analysis*; D011467:Prostate / Q000737:chemistry / Q000473:pathology; D019048:Prostatic Intraepithelial Neoplasia / Q000737:chemistry / Q000473:pathology; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology; D011494:Protein Kinases / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase