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.
Zamorano
Absalom
A
Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, México, DF.
Lamas
Mónica
M
Vergara
Paula
P
Naranjo
José R
JR
Segovia
José
J
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D058851:GPI-Linked Proteins; D015870:Gene Expression / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000494:pharmacology; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006836:Hydro-Lyases / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D011401:Promoter Regions, Genetic; D051381:Rats; D019311:Staurosporine / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D001616:beta-Galactosidase / Q000378:metabolism
D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; C096192:GAS1 protein, human; D058851:GPI-Linked Proteins; C501181:Gas1 protein, rat; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D001616:beta-Galactosidase; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D006836:Hydro-Lyases; C045581:lactate dehydratase; D019311:Staurosporine