Expression quantitative trait loci and receptor pharmacology implicate Arg1 and the GABA-A receptor as therapeutic targets in neuroblastoma

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 KhanAllan Balmain, Qi Wen Fan, William A. Weiss

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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 benzodiazepinemediated 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.

Original languageEnglish (US)
Pages (from-to)1034-1046
Number of pages13
JournalCell Reports
Volume9
Issue number3
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

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Quantitative Trait Loci
GABA-A Receptors
Neuroblastoma
Tumors
Pharmacology
gamma-Aminobutyric Acid
Arginase
Neurology
Benzodiazepines
Gene expression
Neoplasms
Sympathetic Nervous System
Peripheral Nervous System
Therapeutics
Chemical activation
Peripheral Nerves
Apoptosis
Gene Expression
Growth

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Expression quantitative trait loci and receptor pharmacology implicate Arg1 and the GABA-A receptor as therapeutic targets in neuroblastoma. / Hackett, Christopher S.; Quigley, David A.; Wong, Robyn A.; Chen, Justin; Cheng, Christine; Song, Young K.; Wei, Jun S.; Pawlikowska, Ludmila; Bao, Yun; Goldenberg, David D.; Nguyen, Kim; Clay Gustafson, W.; Rallapalli, Sundari K.; Cho, Yoon-Jae; Cook, James M.; Kozlov, Serguei; Mao, Jian Hua; Van Dyke, Terry; Kwok, Pui Yan; Khan, Javed; Balmain, Allan; Fan, Qi Wen; Weiss, William A.

In: Cell Reports, Vol. 9, No. 3, 01.01.2014, p. 1034-1046.

Research output: Contribution to journalArticle

Hackett, CS, Quigley, DA, Wong, RA, Chen, J, Cheng, C, Song, YK, Wei, JS, Pawlikowska, L, Bao, Y, Goldenberg, DD, Nguyen, K, Clay Gustafson, W, Rallapalli, SK, Cho, Y-J, Cook, JM, Kozlov, S, Mao, JH, Van Dyke, T, Kwok, PY, Khan, J, Balmain, A, Fan, QW & Weiss, WA 2014, 'Expression quantitative trait loci and receptor pharmacology implicate Arg1 and the GABA-A receptor as therapeutic targets in neuroblastoma', Cell Reports, vol. 9, no. 3, pp. 1034-1046. https://doi.org/10.1016/j.celrep.2014.09.046
Hackett, Christopher S. ; Quigley, David A. ; Wong, Robyn A. ; Chen, Justin ; Cheng, Christine ; Song, Young K. ; Wei, Jun S. ; Pawlikowska, Ludmila ; Bao, Yun ; Goldenberg, David D. ; Nguyen, Kim ; Clay Gustafson, W. ; Rallapalli, Sundari K. ; Cho, Yoon-Jae ; Cook, James M. ; Kozlov, Serguei ; Mao, Jian Hua ; Van Dyke, Terry ; Kwok, Pui Yan ; Khan, Javed ; Balmain, Allan ; Fan, Qi Wen ; Weiss, William A. / Expression quantitative trait loci and receptor pharmacology implicate Arg1 and the GABA-A receptor as therapeutic targets in neuroblastoma. In: Cell Reports. 2014 ; Vol. 9, No. 3. pp. 1034-1046.
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AU - Song, Young K.

AU - Wei, Jun S.

AU - Pawlikowska, Ludmila

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AU - Goldenberg, David D.

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AU - Clay Gustafson, W.

AU - Rallapalli, Sundari K.

AU - Cho, Yoon-Jae

AU - Cook, James M.

AU - Kozlov, Serguei

AU - Mao, Jian Hua

AU - Van Dyke, Terry

AU - Kwok, Pui Yan

AU - Khan, Javed

AU - Balmain, Allan

AU - Fan, Qi Wen

AU - Weiss, William A.

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