Activation of neurotrophin-3 receptor TrkC induces apoptosis in medulloblastomas |
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Authors: | JY Kim ME Sutton DJ Lu TA Cho LC Goumnerova L Goritchenko JR Kaufman KK Lam AL Billet NJ Tarbell J Wu JC Allen CD Stiles RA Segal SL Pomeroy |
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Affiliation: | Department of Neurology, Children's Hospital, Boston, Massachusetts 02115, USA. |
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Abstract: | Elevated expression of the neurotrophin-3 (NT-3) receptor TrkC by childhood medulloblastomas is associated with favorable clinical outcome. Here, we provide 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 growth of intracerebral xenografts of a medulloblastoma cell line in nude mice; and (c) trkC expression by individual tumor cells is highly correlated with apoptosis within primary medulloblastoma biopsy specimens. TrkC-mediated NT-3 signaling promotes apoptosis by activating multiple parallel signaling pathways and by inducing immediate-early gene expression of both c-jun and c-fos. Considered collectively, these results support the conclusion that the biological actions of TrkC activation affect medulloblastoma outcome by inhibiting tumor growth through the promotion of apoptosis. |
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