Journal article
IGF-IR dependent expression of Survivin is required for T-Antigen mediated Protection from Apoptosis and Proliferation of Neural Progenitors
Cell death and differentiation, v 17(3), pp 439-451
01 Mar 2010
PMID: 19834489
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The Insulin-like Growth Factor-1 Receptor (IGF-IR) and the human
polyomavirus
JCV protein, T-Antigen cooperate in the transformation of neuronal precursors in the cerebellum, which may be a contributing factor in the development of brain tumors. Since it is not clear why T-Antigen requires IGF-IR for transformation, we investigated this process in neural progenitors from IGF-IR knockout embryos (ko-IGF-IR) and from their wild type non-transgenic littermates (wt-IGF-IR). In contrast to wt-IGF-IR, the brain and dorsal root ganglia of ko-IGF-IR embryos showed low levels of the anti-apoptotic protein Survivin, accompanied by elevated numbers of apoptotic neurons and an earlier differentiation phenotype. In wt-IGF-IR neural progenitors
in vitro
, induction of T-Antigen expression tripled the expression of Survivin, and accelerated cell proliferation. In ko-IGF-IR progenitors induction of T-Antigen failed to increase Survivin, resulting in massive apoptosis. Importantly, ectopic expression of Survivin protected ko-IGF-IR progenitor cells from apoptosis and siRNA inhibition of Survivin activated apoptosis in wt-IGF-IR progenitors expressing T-Antigen. Our results indicate that reactivation of the anti-apoptotic Survivin may be a critical step in JCV T-Antigen induced transformation, which in neural progenitors requires IGF-IR.
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Details
- Title
- IGF-IR dependent expression of Survivin is required for T-Antigen mediated Protection from Apoptosis and Proliferation of Neural Progenitors
- Creators
- Elisa Gualco - Temple UniversityKatarzyna Urbanska - Temple UniversityGeorgina Perez-Liz - Temple UniversityThersa Sweet - Temple UniversityFrancesca Peruzzi - Temple UniversityKrzysztof Reiss - Temple UniversityLuis Del Valle - Temple University
- Publication Details
- Cell death and differentiation, v 17(3), pp 439-451
- Publisher
- Springer Nature
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Epidemiology and Biostatistics; A.J. Drexel Autism Institute
- Web of Science ID
- WOS:000274565300007
- Scopus ID
- 2-s2.0-76749106495
- Other Identifier
- 991021448044904721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology