Effects of cotransfection of antisense-EGFR and wild-type PTEN cDNA on human glioblastoma cells.
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.
Tian
Xin-Xia
XX
Department of Pathology, Peking University Health Science Center, Beijing 100083, China. tianxinxia@yahoo.com
Zhang
Yun-Gang
YG
Du
Juan
J
Fang
Wei-Gang
WG
Ng
Ho-Keung
HK
Zheng
Jie
J
D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D016373:DNA, Antisense; D018076:DNA, Complementary; D004815:Epidermal Growth Factor / Q000235:genetics* / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000378:metabolism; D014162:Transfection
D016373:DNA, Antisense; D018076:DNA, Complementary; D005904:Glial Fibrillary Acidic Protein; D004815:Epidermal Growth Factor; D019098:Telomerase; D051059:PTEN Phosphohydrolase