Expression Quantitative Trait Loci and Receptor Pharmacology Implicate Arg1 and the GABA-A Receptor as Therapeutic Targets in Neuroblastoma
oleh: Christopher S. Hackett, David A. Quigley, Robyn A. Wong, Justin Chen, Christine Cheng, Young K. Song, Jun S. Wei, Ludmila Pawlikowska, Yun Bao, David D. Goldenberg, Kim Nguyen, W. Clay Gustafson, Sundari K. Rallapalli, Yoon-Jae Cho, James M. Cook, Serguei Kozlov, Jian-Hua Mao, Terry Van Dyke, Pui-Yan Kwok, Javed Khan, Allan Balmain, QiWen Fan, William A. Weiss
| Format: | Article |
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| Diterbitkan: | Elsevier 2014-11-01 |
Deskripsi
The development of targeted therapeutics for neuroblastoma, the third most common tumor in children, has been limited by a poor understanding of growth signaling mechanisms unique to the peripheral nerve precursors from which tumors arise. In this study, we combined genetics with gene-expression analysis in the peripheral sympathetic nervous system to implicate arginase 1 and GABA signaling in tumor formation in vivo. In human neuroblastoma cells, either blockade of ARG1 or benzodiazepine-mediated activation of GABA-A receptors induced apoptosis and inhibited mitogenic signaling through AKT and MAPK. These results suggest that ARG1 and GABA influence both neural development and neuroblastoma and that benzodiazepines in clinical use may have potential applications for neuroblastoma therapy.