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| Status |
Public on Jun 06, 2018 |
| Title |
Gene expression changes in HEI-193 (NF2-deficient Schwannoma) cells by NF2-restoring or TEW7197 treatment. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Neurofibromatosis type 2 (NF2) syndrome is a very rare human genetic disease and until now, it’s proper treatment has not been suggested. In our recent study, it has been reported that the loss of NF2 activates MAPK signaling through reduction of RKIP in a mesothelioma model. Here, we show that loss of NF2 induces reduction of the TGF-β receptor 2 (TβR2) expression and an overwhelming expression of TGF-β receptor 1 is activated by physical stimuli such as pressure or heavy materials. Activated TR1 induced the phosphorylation and degradation of RKIP. RKIP reduction consequently results in MAPK activation as well as Snail-mediated p53 suppression and occurrence of EMT in NF2-deficient cells by physical stimuli. Thus, TβR1 kinase inhibitors restore cell differentiation and induce growth suppression in NF2 deficient Schwannoma cell line and MEF. Moreover, TEW7197, a specific TβR1 kinase inhibitor, reduces tumor formation in the NF2-model mouse (Postn-Cre;NF2f/f). Gene expression profiling reveals that TEW7197-treatment induces the expression of lipid metabolism-related gene set such as NF2-restored cells in HEI-193 (NF2-deficient Schwannoma). Our results indicate that reduction or deletion of TβR2 or NF2 induces the TβR1-mediated oncogenic pathway, and therefore inhibition of the unbalanced TGF-β signaling is a putative strategy for NF2-related cancers (NF2 syndrome and mesothelioma) and TβR2 mutated advanced cancers.
To know the global effect of TEW7197, we performed the microarray with HEI-193.
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| Overall design |
For differential gene expression analysis by NF2 transfection and TEW7197 treatment, microarray was performed using the Affymetrix GeneChip (Human Gene 2.0 ST Array; DNA Link, Inc, Korea). Total RNA obtained from HEI-193 transfected with NF2 (about 60% transfection yield) or treated with TEW7197 (10 M for 12 hr or 24 hr) was quantified and used for analysis. For differentially expressed gene (DEG) analysis, probes were selected if the difference in expressions were 1.5 fold compared to the HEI-193 control, and were statistically filtered by t-test (p<0.05). For the functional analysis, only DEG probes were used. Web tool DAVID (david.abcc.ncifcrf.gov/home.jsp), data base of which are Gene Ontology, KEGG, BIOCARTA and OMIM_DISEAE, was used for functional grouping of probes. All statistical and functional analysis were performed by DNA Link, Inc.
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| Contributor(s) |
Cho J, Oh A, Park S, Kang S, Yoon M, Woo T, Park B |
| Citation(s) |
30135214 |
| Submission date |
Jun 05, 2018 |
| Last update date |
Mar 15, 2019 |
| Contact name |
Bum-Joon Park |
| E-mail(s) |
bjpark1219@pusan.ac.kr
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| Phone |
82-51-510-2220
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| Organization name |
Pusan National University
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| Department |
Molecular Biology
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| Lab |
Lab of Cancer Research
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| Street address |
Busandaehak-ro 63
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| City |
BUSAN |
| ZIP/Postal code |
609-735 |
| Country |
South Korea |
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| Platforms (1) |
| GPL16686 |
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA474687 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE115359_1._DEG.xlsx |
14.1 Mb |
(ftp)(http) |
XLSX |
| GSE115359_2._DEG.xlsx |
14.0 Mb |
(ftp)(http) |
XLSX |
| GSE115359_3._DEG.xlsx |
14.0 Mb |
(ftp)(http) |
XLSX |
| GSE115359_RAW.tar |
30.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
| Processed data are available on Series record |
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