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Updated: Jun 1, 2026
miRNA Expression Analyses in Prostate Cancer Clinical Tissues
Published on: September 8, 2015
mTOR-RAPTOR and 14-3-3σ immunohistochemical expression in high grade prostatic intraepithelial neoplasia and
Sevan Evren1, Arthur Dermen, Gina Lockwood
1Department of Laboratory Medicine, University Health Network, Toronto, Ontario, Canada.
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.
Insights
14-3-3σ inhibits mTOR activity in the prostate, showing an inverse correlation with phosphorylated mTOR (p-mTOR) in prostate cancer progression. This finding may guide the use of mTOR inhibitors for prostate cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- The mammalian target of rapamycin (mTOR) pathway regulates protein synthesis and growth, and is often dysregulated in cancers.
- mTORC1 complex, formed by mTOR and RAPTOR, is crucial for mTOR pathway activation.
- 14-3-3σ protein is known to modulate mTOR-RAPTOR interactions and signaling.
Purpose of the Study:
- To investigate the expression patterns of phosphorylated mTOR (p-mTOR), RAPTOR, and 14-3-3σ in high-grade prostatic intraepithelial neoplasia (HGPIN) and prostate adenocarcinoma (PCa).
- To explore the potential role of 14-3-3σ as a regulator of mTOR activity in prostate cancer development.
Main Methods:
- Utilized tissue microarrays for immunohistochemical analysis of p-mTOR, RAPTOR, and 14-3-3σ expression.
- Applied Cochran-Armitage analysis to assess expression trends across different grades of prostate lesions.
Main Results:
- Observed distinct expression patterns for mTOR and 14-3-3σ between HGPIN and PCa.
- Demonstrated a decrease in p-mTOR and an increase in 14-3-3σ expression with progression from PIN to high-grade PCa.
- Found that p-mTOR and 14-3-3σ staining occupied different areas within the same tissue core when co-expressed.
Conclusions:
- The inverse correlation between p-mTOR and 14-3-3σ suggests 14-3-3σ acts as an inhibitor of p-mTOR in the prostate.
- Individual patient expression levels of 14-3-3σ and mTOR may predict the efficacy of mTOR inhibitors as therapeutic agents for prostate cancer.
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