title: mTOR-RAPTOR and 14-3-3σ immunohistochemical expression in high grade prostatic intraepithelial neoplasia and prostatic adenocarcinomas: a tissue microarray study.
abstract: BACKGROUND
  The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase which associates with regulatory-associated protein of TOR (RAPTOR), forming the mTORC1 complex, which is necessary for activation of the mTOR pathway. 14-3-3σ belongs to a family of proteins known to regulate the mTOR-RAPTOR interaction and signalling of this cascade. The mTOR pathway is a key regulator of protein synthesis and growth and is up-regulated in many cancers. The correlation of mTOR, RAPTOR and 14-3-3σ in high grade prostatic intraepithelial neoplasia (HGPIN) and prostate cancer has not previously been investigated.
  
  
  OBJECTIVE
  To examine the immunohistochemical expression of phosphorylated mTOR (p-mTOR), RAPTOR and 14-3-3σ in HGPIN and prostatic adenocarcinoma (PCa) using tissue microarrays.
  
  
  RESULTS
  There were contrasting immunohistochemical patterns of expression for mTOR and 14-3-3σ in HGPIN and PCa. Cochran-Armitage analysis demonstrated decreasing p-mTOR and increasing 14-3-3σ expression, progressing from PIN through GL6 and GL7 to high grade PCa. In cores with coexistent staining for 14-3-3σ and p-mTOR, the expression of each marker was restricted to different geographical areas of an individual core.
  
  
  CONCLUSIONS
  The inverse correlation of p-mTOR and 14-3-3σ expression supports the role of 14-3-3σ as an inhibitor of p-mTOR activity in the prostate. The extent of 14-3-3σ and mTOR expression in an individual patient with prostate cancer would determine how effective the use of mTOR inhibitors would be as potential therapeutic agents.
authors.affiliation: Department of Laboratory Medicine, University Health Network, Toronto, Ontario, Canada.
authors.forename: Sevan
authors.initials: S
authors.lastname: Evren
authors.forename: Arthur
authors.initials: A
authors.lastname: Dermen
authors.forename: Gina
authors.initials: G
authors.lastname: Lockwood
authors.forename: Neil
authors.initials: N
authors.lastname: Fleshner
authors.forename: Joan
authors.initials: J
authors.lastname: Sweet
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism / Q000502:physiology*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism / Q000502:physiology*; D005092:Exonucleases / Q000378:metabolism / Q000502:physiology*; D005095:Exoribonucleases; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D046228:Microarray Analysis; D010766:Phosphorylation; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D000076223:Regulatory-Associated Protein of mTOR; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D048948:14-3-3 Proteins; D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C463659:RPTOR protein, human; D000076223:Regulatory-Associated Protein of mTOR; D058570:TOR Serine-Threonine Kinases; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human