Role of PTEN in cholera toxin-induced SWO-38 glioma cell differentiation

摘要

Malignant gliomas persist as a major disease responsible for high morbidity and mortality rates in adults. Differentiation therapy has emerged as a promising treatment modality. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene function is commonly lost in primary gliomas, particularly in glioblastomas, and this is associated with tumor differentiation. PTEN gene deletion is one of the main molecular events in gliomas. In this study, we aimed to explore the effect and mechanisms of PTEN on cholera toxin (CT)-induced SWO-38 glioma cell differentiation. It has been shown that transfection of the exogenous PTEN gene induces glioma cell differentiation; however, the underlying mechanism remains to be elucidated. Results of the present study showed that CT-induced SWO-38 glioma cell differentiation was characterized by morphological changes, the increased expression of glial fibrillary acidic protein (GFAP), an accumulation of cells in the G0/G1 phase of the cell cycle, the decreased expression of cyclin D1 and a decreased invasion and migration capacity. Silencing of the PTEN protein using RNA interference resulted in suppressed cell differentiation. Furthermore, inhibition of the PI3K/AKT pathway by the inhibitor LY294002 led to attenuated differentiation, while differentiation remained stable with the inhibition of the MAPK/ERK pathway by PD0325901. Thus, PTEN may be important in glioma cell differentiation.