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01.05.2011 | Laboratory Investigation - Human/Animal Tissue

Wilms’ tumor 1 silencing decreases the viability and chemoresistance of glioblastoma cells in vitro: a potential role for IGF-1R de-repression

verfasst von: Mike Y. Chen, Aaron J. Clark, Dana C. Chan, Joy L. Ware, Shawn E. Holt, Archana Chidambaram, Helen L. Fillmore, William C. Broaddus

Erschienen in: Journal of Neuro-Oncology | Ausgabe 1/2011

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Abstract

Wilms’ tumor 1 (WT1) is a transcription factor with a multitude of downstream targets that have wide-ranging effects in non-glioma cell lines. Though its expression in glioblastomas is now well-documented, the role of WT1 in these tumors remains poorly defined. We hypothesized that WT1 functions as an oncogene to enhance glioblastoma viability and chemoresistance. WT1’s role was examined by studying the effect of WT1 silencing and overexpression on DNA damage, apoptosis and cell viability. Results indicated that WT1 silencing adversely affected glioblastoma viability, at times, in synergy with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and cisplatin. To investigate other mechanisms through which WT1 could affect viability, we measured cell cycle distribution, senescence, and autophagy. WT1 silencing had no effect on these processes. Lastly, we examined WT1 regulation of IGF-1R expression. Counterintuitively, upregulation of IGF-1R was evident after WT1 silencing. In conclusion, WT1 functions as a survival factor in glioblastomas, possibly through inhibition of IGF-1R expression.

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Titel: Wilms’ tumor 1 silencing decreases the viability and chemoresistance of glioblastoma cells in vitro: a potential role for IGF-1R de-repression
verfasst von: Mike Y. Chen
Aaron J. Clark
Dana C. Chan
Joy L. Ware
Shawn E. Holt
Archana Chidambaram
Helen L. Fillmore
William C. Broaddus
Publikationsdatum: 01.05.2011
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 1/2011
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-010-0374-7

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