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Gene expression changes in HEI-193 (NF2-deficient Schwannoma) cells by NF2-restoring or TEW7197 treatment.

ABSTRACT: 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 TR1 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE115359 | GEO | 2018/06/06

REPOSITORIES: GEO

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Gene expression changes in HEI-193 (NF2-deficient Schwannoma) cells by Nf18001 or TEW7197 treatment.

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Gene expression changes in HEI-193 (NF2-deficient Schwannoma) cells by NF2-restoring or TEW7197 treatment.

Project description:Gene expression changes in HEI-193 (NF2-deficient Schwannoma) cells by NF2-restoring or TEW7197 treatment.

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Gene expression changes in HEI-193 (NF2-deficient Schwannoma) cells by Nf18001 or TEW7197 treatment.

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