Targeted-simultaneous expression of Gas1 and p53 using a bicistronic adenoviral vector in gliomas.
The targeted expression of transgenes is one of the principal goals of gene therapy, and it is particularly relevant for the treatment of brain tumors. In this study, we examined the effect of the overexpression of human gas1 (growth arrest specific 1) and human p53 cDNAs, both under the transcriptional control of a promoter of the human glial fibrillary acidic protein (gfa2), employing adenoviral expression vectors, in glioma cells. We showed that the targeted overexpression of gas1 and p53 (AdSGas1 and AdSp53, respectively) in rat glioma cells (C6) reduced the number of viable cells and induced apoptosis. Moreover, the adenovirally targeted expression of these genes also reduced tumor growth in vivo. Unexpectedly, there was no additive effect when both gas1 and p53 were simultaneously expressed in the same cells using a bicistronic adenoviral vector. We suggest that Gas1 does not act in combination with p53 in the C6 and U373 glioma cell lines, inducing apoptosis and cell cycle arrest. Our results indicate that the targeted expression of tumor suppressor genes (gas1 and p53) regulated by the gfa2 promoter, together with adenoviral vectors may provide an interesting approach for adjuvant selective glioma gene therapy.
Benítez
J A
JA
Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, México DF, México.
Arregui
L
L
Vergara
P
P
Segovia
J
J
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D053938:DNA Fragmentation; D058851:GPI-Linked Proteins; D005822:Genetic Vectors; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D005910:Glioma / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D018797:Cell Cycle Proteins; C096192:GAS1 protein, human; D058851:GPI-Linked Proteins; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D016159:Tumor Suppressor Protein p53