mTOR-RAPTOR and 14-3-3 sigma immunohistochemical expression in high grade prostatic intraepithelial neoplasia and prostatic adenocarcinomas: a tissue microarray study

作者：Evren Sevan; Dermen Arthur; Lockwood Gina; Fleshner Neil; Sweet Joan^*

来源：Journal of Clinical Pathology, 2011, 64(8): 683-688.

DOI：10.1136/jclinpath-2011-200083

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. 14-3-3 sigma 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 14-3-3 sigma 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 14-3-3 sigma in HGPIN and prostatic adenocarcinoma (PCa) using tissue microarrays.
Methods and results There were contrasting immunohistochemical patterns of expression for mTOR and 14-3-3 sigma in HGPIN and PCa. Cochran-Armitage analysis demonstrated decreasing p-mTOR and increasing 14-3-3 sigma expression, progressing from PIN through GL6 and GL7 to high grade PCa. In cores with coexistent staining for 14-3-3 sigma 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 14-3-3 sigma expression supports the role of 14-3-3 sigma as an inhibitor of p-mTOR activity in the prostate. The extent of 14-3-3 sigma 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.

• 出版日期2011-8