Xin-Xia Tian 1, Yun-Gang Zhang 1, Juan Du 1, Wei-Gang Fang 1, Ho-Keung Ng 2, and Jie Zheng 1
1 Department of Pathology, Peking University Health Science
Center, Beijing 100083, China.
2 Department of Anatomical and Cellular Pathology, Prince
of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
Department of Pathology, Peking University Health Science Center, Beijing 100083, China.
The main molecular genetic changes identified in glioblastomas are overexpression/amplification of the epidermal growth factor receptor (EGFR) gene and mutation/ deletion of the tumor suppressor PTEN gene. These two genetic changes both play important roles in glial tumorigenesis and progression. In this study, we demonstrated that wild-type PTEN transfection inhibited the growth and transforming ability of U87MG cells by 69.3% and 73.5%, respectively. On the other hand, antisense-EGFR transfection inhibited the growth and transforming phenotype of these cells by 50.3% and 46.8%, respectively. However, cotransfection of U87MG cells with wild-type PTEN and antisense EGFR constructs could inhibit the cellular growth by 91.7%. The transforming phenotype of these cells was completely inhibited. In addition, these cotransfected cells showed a differentiated form and expressed much lower telomerase activity than cells transfected with wild-type PTEN or antisense-EGFR alone. In summary, these results suggest that cotransfection is a better approach to suppress glioma cell growth than wild-type PTEN transfer or antisense-EGFR transfection alone. This approach may prove useful as an adjunct therapy in the treatment of glioblastomas.
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