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In contrast to non\u2010neoplastic SCs, VS cells survive long\u2010term in the absence of axons. We find that p75<jats:sup>NTR<\/jats:sup> is overexpressed in VSs compared with normal nerves, both at the transcript and protein level, similar to the response of non\u2010neoplastic SCs following axotomy. Despite elevated p75<jats:sup>NTR<\/jats:sup> expression, VS cells are resistant to apoptosis due to treatment with proNGF, a high affinity ligand for p75<jats:sup>NTR<\/jats:sup>. Furthermore, treatment with proNGF protects VS cells from apoptosis due to c\u2010Jun N\u2010terminal kinase (JNK) inhibition indicating that p75<jats:sup>NTR<\/jats:sup> promotes VS cell survival. Treatment of VS cells with proNGF activated NF\u2010\u03baB while inhibition of JNK with SP600125 or siRNA\u2010mediated knockdown reduced NF\u2010\u03baB activity. Significantly, proNGF also activated NF\u2010\u03baB in cultures treated with JNK inhibitors. Thus, JNK activity appears to be required for basal levels of NF\u2010\u03baB activity but not for proNGF\u2010induced NF\u2010\u03baB activity. To confirm that the increase in NF\u2010\u03baB activity contributes to the prosurvival effect of proNGF, we infected VS cultures with Ad.I\u03baB.SerS32\/36A virus, which inhibits NF\u2010\u03baB activation. Compared with control virus, Ad.I\u03baB.SerS32\/36A significantly increased apoptosis including in VS cells treated with proNGF. Thus, in contrast to non\u2010neoplastic SCs, p75<jats:sup>NTR<\/jats:sup> signaling provides a prosurvival response in VS cells by activating NF\u2010\u03baB independent of JNK. Such differences may contribute to the ability of VS cells to survive long\u2010term in the absence of axons. 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