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Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures
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Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures

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Signal transduction molecules in gliomas of all grades

Ralph P Ermoian1, Tania Kaprealian, Kathleen R Lamborn

  • 1Department of Radiation Oncology, The University of California, San Francisco, 1600 Divisadero St. Suite H1031, San Francisco, CA, 94143-1708, USA.

Journal of Neuro-Oncology
|September 2, 2008
PubMed
Abstract

Insights

Key signaling molecules in the PI3-kinase pathway, upstream and downstream of mTOR, differ in gliomas. This suggests mTOR is a therapeutic target for all glioma grades.

Area of Science:

  • Neuro-oncology
  • Molecular Biology
  • Cancer Signaling Pathways

Background:

  • Gliomas are primary brain tumors with varying grades (II, III, IV).
  • The phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is crucial in cell growth and survival.
  • Dysregulation of this pathway is implicated in various cancers, including gliomas.

Purpose of the Study:

  • To investigate the expression of critical effectors in the PI3K pathway, both upstream and downstream of mTOR, in different grades of gliomas.
  • To compare these molecular profiles with non-tumor brain tissue.

Main Methods:

  • Analysis of tumor and non-tumor brain specimens from 87 patients.
  • Quantification of protein levels using immunoblots.
  • Assessment of RNA levels via polymerase chain reaction (PCR) amplification.
  • Statistical analysis using Spearman's Correlation Coefficient for multiple comparisons.

Main Results:

  • Expression levels of phosphorylated-4E-BP1, phosphorylated-PKB/Akt, PTEN, TSC1, and TSC2 significantly correlated with glioma grade (P < 0.01).
  • Lower levels of TSC1 and TSC2 messenger RNA (mRNA) were observed in glioblastoma multiforme (GBM) compared to grade II gliomas and non-tumor brain.
  • Phosphorylated-S6 expression did not differ significantly between non-tumor brain and gliomas of any grade.

Conclusions:

  • Expression patterns of key PI3K pathway molecules differ across glioma grades and compared to normal brain tissue.
  • The lack of difference in phosphorylated-S6 suggests involvement of other kinases in S6 phosphorylation.
  • mTOR represents a viable therapeutic target for gliomas, potentially enhanced by combination therapies.

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