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

• Published in: Anticancer research Vol. 31; no. 9; pp. 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: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01.09.2011
• 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; Extracellular signal-regulated protein kinase; type I insulin-like growth factor receptor; Gastrointestinal stromal tumor; Cancerology; PI3K-Akt/mTOR pathway; insulin-like growth factor 1 receptor (IGF1R); Intestinal disease; CD117; Ras-Raf-ERK/MAPK Pathway; Protooncogene; Gastric disease; Biological receptor; Enzyme; Transferases; Akt protein kinase; Mitogen-activated protein kinase; Malignant tumor; Insulin like growth factor 1; 1-Phosphatidylinositol 3-kinase; C-Onc gene; Mammalian target of rapamycin; Digestive diseases; Gastrointestinal stromal tumors (GISTs); Ras gene; Cancer
• ISSN: 0250-7005; 1791-7530

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.