Activation of neurotrophin-3 receptor TrkC induces apoptosis in medulloblastomas

Elevated expression of the neurotrophin-3 (NT-3) receptor TrkC by childhood medulloblastomas is associated with favorable clinical outcome. Here, we p rovide evidence that TrkC is more than simply a passive marker of prognosis . We demonstrate that: (a) medulloblastomas undergo apoptosis in vitro when grown in the presence of NT-3; (b) overexpression of TrkC inhibits the gro wth of intracerebral xenografts of a medulloblastoma cell line in nude mice ; and (c) trkC expression by individual tumor cells is highly correlated wi th apoptosis within primary medulloblastoma biopsy specimens. TrkC-mediated NT-3 signaling promotes apoptosis by activating multiple parallel signalin g pathways and by inducing immediate-early gene expression of both c-jun an d c-fos. Considered collectively, these results support the conclusion that the biological actions of TrkC activation affect medulloblastoma outcome b y inhibiting tumor growth through the promotion of apoptosis.