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Series GSE40187 Query DataSets for GSE40187
Status Public on Jun 06, 2013
Title Therapeutic potential of a novel HSP90 Inhibitor, NXD30001, for Neurofibromatosis type 2
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Purpose: The growth and survival of NF2-deficient cells are enhanced by the activation of multiple signaling pathways including ErbB2/IGF-1R/Met, PI3K/Akt, and Ras/Raf/Mek/Erk1/2. The ubiquitously expressed chaperone protein HSP90 is known to be essential for the stabilization of these signaling molecules. We aim to evaluate the effect of the HSP90 inhibition on the signaling pathways activated in NF2-related tumors. We tested the efficacy of the newly synthesized small molecule NXD30001 which was shown to be more potent in HSP90 inhibition in vitro and less toxic in vivo than already existing HSP90 inhibitors.
Experimental Design: The anti-proliferative activity of NXD30001 was tested in NF2-deficient mouse cells in vitro, and its anti-tumor efficacy was verified in an NF2-deficient allograft model in vivo. The underlying molecular alteration in vitro and in vivo was further characterized by a global transcriptome approach.
Results: NXD30001 was found to induce degradation of client proteins and to suppress proliferation in NF2-deficient cells in vitro and in vivo. Differential expression analysis further identified subsets of genes implicated in cell proliferation, survival, vascularization, and Schwann cell differentiation, whose expression were altered by NXD30001 treatment.
Conclusions: NXD30001 is a potent HSP90 inhibitor showing significant antitumor activity against NF2-related tumor cells in vitro and in vivo, and represents a promising option for novel NF2 therapies.
Overall design Global RNA expression in NXD30001-treated and untreated matched NF2-deficiemt cultured cells (in vitro) and allograft tumors (in vivo) were compared by RNA-Seq.
Contributor(s) Giovannini M, Tanaka K, Eskin A
Citation(s) 23714726
Submission date Aug 17, 2012
Last update date May 15, 2019
Contact name Ascia Eskin
Organization name UCLA
Department Human Genetics
Lab Stanley Nelson
Street address 695 Charles Young Drive South Gonda 5554
City Los Angeles
State/province California
ZIP/Postal code 90095-7088
Country USA
Platforms (2)
GPL9250 Illumina Genome Analyzer II (Mus musculus)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (4)
GSM988040 ESC-FC1801 In Vivo-Control
GSM988041 ESC-FC1801 In Vivo-Treated
GSM988042 ESC-FC1801 In Vitro-Control (MG1)
BioProject PRJNA173039
SRA SRP014901

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Supplementary file Size Download File type/resource
GSE40187_gene_exp_diff_Control_NXD30001_fromtophat120_cufflinks102_c0_081612.txt.gz 1.4 Mb (ftp)(http) TXT
GSE40187_gene_exp_diff_MG1_MG2_fromtophat120_cufflinks102_c0_081612.txt.gz 1.3 Mb (ftp)(http) TXT
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