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mTOR–RAPTOR and 14-3-3σ immunohistochemical expression in high grade prostatic intraepithelial neoplasia and prostatic adenocarcinomas: a tissue microarray study
  1. Sevan Evren1,2,
  2. Arthur Dermen1,2,
  3. Gina Lockwood3,
  4. Neil Fleshner1,2,
  5. Joan Sweet1,2
  1. 1Department of Laboratory Medicine, University Health Network, Toronto, Ontario, Canada
  2. 2Department of Surgery, University Health Network, Toronto, Ontario, Canada
  3. 3Knowledge Management Division, Canadian Partnership Against Cancer, Toronto, Ontario, Canada
  1. Correspondence to Dr Joan Sweet, General Hospital, Eaton North Wing, 11th Floor, Room 11EN224, 200 Elizabeth St, Toronto, ON M5G 2C4, Canada; joan.sweet{at}uhn.on.ca

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.

Aims To examine the immunohistochemical expression of phosphorylated mTOR (p-mTOR), RAPTOR and 14-3-3σ in HGPIN and prostatic adenocarcinoma (PCa) using tissue microarrays.

Methods and 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.

Conclusion 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.

  • mTOR
  • RAPTOR
  • 14-3-3σ
  • immunohistochemistry
  • tissue microarray
  • prostate adenocarcinomas
  • high grade prostatic intraepithelial neoplasia
  • prostate
  • renal
  • neoplasms

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Footnotes

  • Competing interests None.

  • Ethics approval University Health Network research ethics board approval was obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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