Transcriptionally mediated gene targeting of gas1 to glioma cells elicits growth arrest and apoptosis.

Induction of growth arrest-specific genes (gas1) prevents cell proliferation and/or leads to apoptosis in different cell types. In neurons, it has been recently reported that mild excitotoxic neuronal death is associated with gas1 induction, and that overexpression of Gas1 induces apoptosis in terminally differentiated neurons or in proliferating neuroblastoma cells. In the present study, we have analysed the effects of the transcriptionally mediated targeting of gas1 to C6 rat glioma cells. Expression of Gas1 decreased glial proliferation and induced C6 cell apoptosis. While the identity of the caspase(s) responsible for Gas1-induced apoptosis in neurons has remained elusive, in C6 glioma cells, overexpression of Gas1 reproducibly activated caspase-3. Our results support the concept of targeted expression of gas1 as a potentially useful gene therapy strategy in the treatment of human gliomas. Copyright 2002 Wiley-Liss, Inc.