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mTOR, S6 and AKT expression in relation to proliferation and apoptosis/autophagy in glioma

Laura Annovazzi1, Marta Mellai, Valentina Caldera

  • 1Neuro-bio-oncology Center of Policlinico di Monza Foundation/University of Turin, Vercelli, Italy.

Anticancer Research
|August 8, 2009
PubMed
Abstract

Insights

The study found that ribosomal S6 kinase (S6K1) expression correlates with proliferation markers in human gliomas, highlighting its role downstream of the PI3/AKT pathway. This suggests S6K1 is important for glioma growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • The mammalian target of rapamycin (mTOR) pathway regulates cell growth and is implicated in malignant glioma.
  • mTOR can be activated by protein kinase B (AKT) or ribosomal S6 kinase (S6K1), and mTOR inhibitors show anti-cancer effects.
  • Understanding the PI3K/AKT/mTOR pathway's role in glioma proliferation and apoptosis is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the relationship between the PI3K/AKT cascade, mTOR, proliferation, and apoptosis in human gliomas.
  • To evaluate the expression levels of key proteins including AKT, mTOR, S6, and apoptosis markers in gliomas of varying grades.

Main Methods:

  • Analysis of 64 gliomas (high- and low-grade) using molecular biology techniques.
  • Quantitative immunohistochemistry and Western blotting were employed to assess protein expression.
  • Key markers studied included AKT, mTOR, S6, caspase-3, PARP1, cleaved PARP1, Ki-67/MIB.1, and beclin 1.

Main Results:

  • Expression of phospho-mTOR, phospho-S6, phospho-AKT, and Ki-67/MIB.1 increased with glioma grade.
  • EGFR amplification correlated with AKT expression, which in turn correlated with mTOR expression.
  • S6 expression correlated with proliferation marker Ki-67/MIB.1, particularly in glioblastoma; mTOR did not correlate with proliferation or apoptosis but inversely correlated with beclin 1.

Conclusions:

  • The correlation between S6 expression and proliferation markers underscores the significance of S6K1 downstream of AKT in the PI3K/AKT pathway.
  • The findings suggest that the S6K1/S6 pathway plays a critical role in glioma proliferation.

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