AKT1 and AKT2 Promote Malignant Transformation in Human

OBJECTIVE To confirm the role played by AKT1 and AKT2 in the b-catenin/Tcf-4 signaling pathway in promoting malignant transfor-mation of glioma cells. METHODS LN229 cells were divided into five groups: a control group, acetone (ACE)group, acetylsalicylic acid (ASA; aspirin) group, ASA+AKT1 plasmid group and ASA+AKT2 plasmid group. Western blot and PCR were used to detect the expression of AKT1 and AKT2 after dealing with ASA and transferring AKT1/2 genes into LN229 cells. Cell proliferation was determined by flow cytometry, cell invasion was evaluated by transwell assay and cell apoptosis was detected with annexin V staining. The molecules regulating proliferation and invasion were examined by western blot analysis. RESULTS Aspirin down-regulates AKT1 and AKT2 expression by modulating b-catenin/Tcf-4 activity. AKT1 and AKT2 can enhance cell proliferation and invasion by up-regulating the expression of cyclin-D and matrix metalloprotein-9 (MMP-9) in LN229 glioma cells. CONCLUSION AKT1 and AKT2 play an important role in the b-catenin/Tcf-4 signaling pathway promoting malignant transforma-tion; AKT1 is more effective than AKT2. AKT1 and AKT2 may be potential targets for brain glioma therapy and an effective way to prevent metastasis of gliomas. KEY WORDS: AKT1, AKT2, brain glioma, malignant transformation