Expression quantitative trait loci and receptor pharmacology implicate Arg1 and the GABA-A receptor as therapeutic targets in neuroblastoma. Cell Rep 2014 Nov 06;9(3):1034-46
Date
12/02/2014Pubmed ID
25437558Pubmed Central ID
PMC4251494DOI
10.1016/j.celrep.2014.09.046Scopus ID
2-s2.0-84919718171 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
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.
Author List
Hackett CS, Quigley DA, Wong RA, Chen J, Cheng C, Song YK, Wei JS, Pawlikowska L, Bao Y, Goldenberg DD, Nguyen K, Gustafson WC, Rallapalli SK, Cho YJ, Cook JM, Kozlov S, Mao JH, Van Dyke T, Kwok PY, Khan J, Balmain A, Fan Q, Weiss WAAuthor
James M. Cook PhD University Distinguished Professor in the Chemistry and Biochemistry department at University of Wisconsin - MilwaukeeMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Arginase
Brain Neoplasms
Cell Line, Tumor
Cell Survival
Chromosomes, Mammalian
Gene Expression Regulation, Neoplastic
Genetic Association Studies
Genetic Linkage
Genetic Predisposition to Disease
Humans
Mice
Molecular Targeted Therapy
Neuroblastoma
Quantitative Trait Loci
Receptors, GABA-A
Survival Analysis
gamma-Aminobutyric Acid
