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Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor
07:21

Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor

Published on: May 2, 2022

Differential activation of MAPK and PI3K/AKT/mTOR pathways and IGF1R expression in gastrointestinal stromal tumors

M J Ríos-Moreno1, S Jaramillo, M Díaz-Delgado

  • 1Department of Pathology, University Hospital Virgen Macarena, Seville, Spain.

Anticancer Research
|August 27, 2011
PubMed
Abstract

Insights

Mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K/Akt/mTOR) pathways differ between mutant and wild-type gastrointestinal stromal tumors (GISTs). PDGFRA-mutated GISTs showed increased PI3K/Akt/mTOR pathway activation, while IGF1R expression was not correlated with pathway activation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gastrointestinal Pathology

Background:

  • Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract.
  • Understanding the molecular pathways involved in GIST pathogenesis is crucial for targeted therapy development.
  • Mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K/Akt/mTOR) signaling pathways are frequently dysregulated in various cancers, including GISTs.

Purpose of the Study:

  • To delineate the differential activation of MAPK and PI3K/Akt/mTOR pathways in mutant (m) versus wild-type (wt) GISTs.
  • To investigate the potential role of insulin-like growth factor 1 receptor (IGF1R) expression in GIST signaling.
  • To correlate pathway activation with specific GIST mutational status.

Main Methods:

  • Immunohistochemical analysis of 99 GIST samples for key pathway markers (phospho-ERK1/2, phospho-Akt, p70S6, 4EBP1, pS6) and IGF1R.
  • Mutation analysis of KIT and PDGFRA genes using PCR and sequencing.
  • Comparative analysis of pathway marker expression between mutant and wild-type GISTs.

Main Results:

  • Significant differences in phospho-ERK1/2 expression were observed between mGISTs and wtGISTs.
  • Overall, the PI3K/Akt/mTOR pathway exhibited greater activation in mGISTs, particularly those with PDGFRA mutations.
  • No significant correlation was found between IGF1R expression and GIST mutational status or pathway activation.

Conclusions:

  • MAPK pathway activation appears absent in wild-type GISTs.
  • GISTs with PDGFRA mutations show a tendency towards PI3K/Akt/mTOR pathway utilization.
  • IGF1R expression is generally low in adult GISTs and does not correlate with MAPK or AKT pathway activation.

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