| First Author | Gualco E | Year | 2010 |
| Journal | Cell Death Differ | Volume | 17 |
| Issue | 3 | Pages | 439-51 |
| PubMed ID | 19834489 | Mgi Jnum | J:169736 |
| Mgi Id | MGI:4941710 | Doi | 10.1038/cdd.2009.146 |
| Citation | Gualco E, et al. (2010) IGF-IR-dependent expression of Survivin is required for T-antigen-mediated protection from apoptosis and proliferation of neural progenitors. Cell Death Differ 17(3):439-51 |
| abstractText | 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. Because 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 nontransgenic 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 antiapoptotic 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 antiapoptotic Survivin may be a critical step in JCV T-antigen-induced transformation, which in neural progenitors requires IGF-IR. |
