BACKGROUND: This study investigated the mechanism underlying the activating mutation of SHP-2 in promoting malignant biological behaviors of glioma cells.

MATERIAL AND METHODS: The SHP-2 empty plasmid pcDNA3.1 and SHP-2 activating mutation plasmid pcDNA3.1 SHP-2 D61G mutant eukaryotic expression vectors were designed; stable SHP-2-expressing cells transfected with pcDNA3.1 SHP-2 D61G mutant were set as the mutation group; cells transfected with pcDNA3.1 were set as the empty vector group; and cells without transfection were set as the control group. The cell reproductive capacity in each group was measured by MTT method. The invasion ability of cells in vitro was detected by Transwell chamber assay, the cell apoptosis in each group was detected by Annexin-V/PE dual-staining method, and the clone formation ability of cells in vitro was detected by Tablet clone-forming assay. The activation of ERK1/2, ARK, and p38MAPK signal pathways in each group was determined by Western blot.

RESULTS: After transfection, the expression of SHP-2 protein in the mutant group was significantly higher than that in the control group and empty vector group. The proliferation ability of transfected cells, the apoptosis rate, the invasion ability, and the expression levels of phosphorylated ERK1/2, AKT, and p38 in the mutation group was significantly higher than in the empty vector group and the control group (P<0.05). Moreover, the cell clone formation ability of the mutation group was obviously enhanced (P<0.05).

CONCLUSIONS: The activating mutation of SHP-2 can lead to malignant changes in biological behaviors of glioma cells, and the specific mechanism may be related to the activation of ERK1/2, AKT, and p38 signal pathway. SHP-2 protein may become a new target for anti-malignant transformation of glioma.

Keywords: Behavior, Addictive, Glioma, Protein Tyrosine Phosphatase, Non-Receptor Type 11