Retroviral delivery and tetracycline-dependent expression of IL-1beta-converting enzyme (ICE) in a rat glioma model provides controlled induction of apoptotic death in tumor cells.
1996; National Institutes of Health; Volume: 56; Issue: 23 Linguagem: Inglês
Autores
John S. Yu, Miguel Sena‐Esteves, Werner Paulus, Xandra O. Breakefield, Steven A. Reeves,
Tópico(s)Retinoids in leukemia and cellular processes
ResumoInterleukin 1beta-converting enzyme (ICE) is a member of a growing family of cysteine proteases shown to be a crucial component in the activation of a genetic program that leads to autonomous cell death in mammalian cells. In this study, a murine ICE-lacZ fusion gene was introduced into a novel retroviral vector designed to achieve regulated ectopic expression of a foreign gene in mammalian cells. By delivering the ICE-lacZ gene within a retroviral vector and under the control of a tetracycline-regulated promoter, we were able to utilize the intrinsic cell death program of ICE as a means for tumoricidal therapy in a rat brain tumor model. Both in culture and in vivo suppression of ICE-lacZ expression was extremely tight in the presence of tetracycline, as determined by the lack of X-galactosidase-positive tumor cells and by cell viability. When tetracycline was withdrawn, ICE-lacZ gene expression was rapidly turned on and apoptosis-mediated cell death occurred in essentially all tumor cells.
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