¹Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, México DF, México

Correspondence: Dr J Segovia, Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, Av. Instituto Politécnico Nacional # 2508, México DF 07360, México. E-mail: jsegovia@fisio.cinvestav.mx

Received 15 March 2007; Revised 8 May 2007; Accepted 27 May 2007; Published online 29 June 2007.

Abstract

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.