TY - JOUR T1 - Expression quantitative trait loci and receptor pharmacology implicate Arg1 and the GABA-A receptor as therapeutic targets in neuroblastoma. JF - Cell Rep Y1 - 2014 A1 - Hackett, Christopher S A1 - Quigley, David A A1 - Wong, Robyn A A1 - Chen, Justin A1 - Cheng, Christine A1 - Song, Young K A1 - Wei, Jun S A1 - Pawlikowska, Ludmila A1 - Bao, Yun A1 - Goldenberg, David D A1 - Nguyen, Kim A1 - Gustafson, W Clay A1 - Rallapalli, Sundari K A1 - Cho, Yoon-Jae A1 - Cook, James M A1 - Kozlov, Serguei A1 - Jiang-Hua Mao A1 - Van Dyke, Terry A1 - Kwok, Pui-Yan A1 - Khan, Javed A1 - Balmain, Allan A1 - Fan, QiWen A1 - Weiss, William A KW - Animals KW - Apoptosis KW - Arginase KW - Brain Neoplasms KW - Cell Line, Tumor KW - Cell Survival KW - Chromosomes, Mammalian KW - gamma-Aminobutyric Acid KW - Gene Expression Regulation, Neoplastic KW - Genetic Association Studies KW - Genetic Linkage KW - Genetic Predisposition to Disease KW - Humans KW - Mice KW - Molecular Targeted Therapy KW - Neuroblastoma KW - Quantitative Trait Loci KW - Receptors, GABA-A KW - Survival Analysis AB -

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.

VL - 9 IS - 3 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25437558?dopt=Abstract ER -