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• W1708804592 endingPage "1712" @default.
• W1708804592 startingPage "1699" @default.
• W1708804592 abstract "Vestibular schwannomas (VSs) arise from Schwann cells (SCs) and result from the loss of function of merlin, the protein product of the NF2 tumor suppressor gene. In contrast to non‐neoplastic SCs, VS cells survive long‐term in the absence of axons. We find that p75 NTR is overexpressed in VSs compared with normal nerves, both at the transcript and protein level, similar to the response of non‐neoplastic SCs following axotomy. Despite elevated p75 NTR expression, VS cells are resistant to apoptosis due to treatment with proNGF, a high affinity ligand for p75 NTR . Furthermore, treatment with proNGF protects VS cells from apoptosis due to c‐Jun N‐terminal kinase (JNK) inhibition indicating that p75 NTR promotes VS cell survival. Treatment of VS cells with proNGF activated NF‐κB while inhibition of JNK with SP600125 or siRNA‐mediated knockdown reduced NF‐κB activity. Significantly, proNGF also activated NF‐κB in cultures treated with JNK inhibitors. Thus, JNK activity appears to be required for basal levels of NF‐κB activity but not for proNGF‐induced NF‐κB activity. To confirm that the increase in NF‐κB activity contributes to the prosurvival effect of proNGF, we infected VS cultures with Ad.IκB.SerS32/36A virus, which inhibits NF‐κB activation. Compared with control virus, Ad.IκB.SerS32/36A significantly increased apoptosis including in VS cells treated with proNGF. Thus, in contrast to non‐neoplastic SCs, p75 NTR signaling provides a prosurvival response in VS cells by activating NF‐κB independent of JNK. Such differences may contribute to the ability of VS cells to survive long‐term in the absence of axons. GLIA 2014;62:1699–1712" @default.
• W1708804592 created "2016-06-24" @default.
• W1708804592 creator A5020269223 @default.
• W1708804592 creator A5034747659 @default.
• W1708804592 creator A5049279431 @default.
• W1708804592 creator A5052105577 @default.
• W1708804592 creator A5073723142 @default.
• W1708804592 creator A5074746982 @default.
• W1708804592 date "2014-06-26" @default.
• W1708804592 modified "2023-10-17" @default.
• W1708804592 title "p75^NTR is highly expressed in vestibular schwannomas and promotes cell survival by activating nuclear transcription factor κB" @default.
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