Differential Activation of MAPK and PI3K/AKT/mTOR Pathways and IGF1R Expression in Gastrointestinal Stromal Tumors

To characterize the differentially-activated mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K/Akt/mTOR) pathways in mutant (m) and wild-type (wt) GISTs and to investigate the role of insulin-like growth factor 1 receptor (IGF1R) expression. Ninety-nine paraffin-embedde...

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Bibliographic Details
Published in:Anticancer research 2011-09, Vol.31 (9), p.3019-3025
Main Authors: RIOS-MORENO, M. J, JARAMILLO, S, DIAZ-DELGADO, M, SANCHEZ-LEON, M, TRIGO-SANCHEZ, I, POLO PADILLO, J, AMERIGO, J, GONZALEZ-CAMPORA, R
Format: Article
Language:English
Subjects:
Base Sequence
Biological and medical sciences
DNA Primers
Enzyme Activation
Gastroenterology. Liver. Pancreas. Abdomen
Gastrointestinal Stromal Tumors - enzymology
Gastrointestinal Stromal Tumors - metabolism
Humans
Medical sciences
Mitogen-Activated Protein Kinases - metabolism
Protein Kinases - metabolism
Receptor, IGF Type 1 - metabolism
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Tumors
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Summary:To characterize the differentially-activated mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K/Akt/mTOR) pathways in mutant (m) and wild-type (wt) GISTs and to investigate the role of insulin-like growth factor 1 receptor (IGF1R) expression. Ninety-nine paraffin-embedded gastrointestinal stromal tumors (GISTs) were selected. CD117, IGF1R, phospho-ERK1/2, phospho-Akt, p70S6, eukaryotic initiation factor 4E-binding protein-1 (4EBP1) and pS6 expression were investigated using immunohistochemical methods. KIT exons 9, 11, 13 and 17 and platelet derived growth factor receptor alpha (PDGFRA) exons 12 and 18 were amplified by PCR and sequenced. Significant differences were found in the expression of phospho-ERK1/2 between mGISTs and wtGISTs. Complex evaluation of all PI3K/Akt/mTOR pathway markers revealed greater activation in mGISTs, particularly in PDGFRA-mutated GISTs. No significant correlation was observed between IGF1R expression and either mutational status or pathway activation. There appears to be no MAPK pathway activation in wtGISTs. Tumors harboring PDGFRA mutations tended to use the PI3K/Akt/mTOR signaling pathway. Most adult GISTs, irrespective of mutational status, displayed no IGFR1 expression; tumors positive for IGFR1 showed no preferential activation of the MAPK or AKT pathways.
ISSN:0250-7005
1791-7530