Activation of neurotrophin-3 receptor TrkC induces apoptosis in medulloblastomas

John Y H Kim; Mary E Sutton; Diane J Lu; Tracey A Cho; Liliana C Goumnerova; Lyuda Goritchenko; Jill R Kaufman; K. K Lam; Amy L Billet; Nancy J Tarbell; Julian WU; Jeffrey C Allen; Charles D Stiles; Rosalind A Segal; Scott L Pomeroy

Activation of neurotrophin-3 receptor TrkC induces apoptosis in medulloblastomas

Journal article

Peer reviewed

Activation of neurotrophin-3 receptor TrkC induces apoptosis in medulloblastomas

John Y H Kim, Mary E Sutton, Diane J Lu, Tracey A Cho, Liliana C Goumnerova, Lyuda Goritchenko, Jill R Kaufman, K. K Lam, Amy L Billet, Nancy J Tarbell, …

Cancer research (Chicago, Ill.), Vol.59(3), pp.711-719

1999

PMID: 9973222

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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.

Neurology

Biological and medical sciences

Medical sciences

Tumors of the nervous system. Phacomatoses

Details

Title: Subtitle: Activation of neurotrophin-3 receptor TrkC induces apoptosis in medulloblastomas
Creators: John Y H Kim - Division of Neuroscience, Department of Neurology, Children 's Hospital, United States
Mary E Sutton - Division of Neuroscience, Department of Neurology, Children 's Hospital, United States
Diane J Lu - Division of Neuroscience, Department of Neurology, Children 's Hospital, United States
Tracey A Cho - Division of Neuroscience, Department of Neurology, Children 's Hospital, United States
Liliana C Goumnerova - Department of Neurosurgery, Children 's Hospital, United States
Lyuda Goritchenko - Department of Neurosurgery, Children 's Hospital, United States
Jill R Kaufman - Division of Neuroscience, Department of Neurology, Children 's Hospital, United States
K. K Lam - Division of Neuroscience, Department of Neurology, Children 's Hospital, United States
Amy L Billet - Department of Pediatric Hematology-Oncology, Dana-Farber Cancer Institute, United States
Nancy J Tarbell - Division of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston Massachusetts 02115, United States
Julian WU - Department of Surgery, Division of Neurosurgery, The Brain Tumor Center, Beth Israel/Deaconess Medical Center, United States
Jeffrey C Allen - Division of Neuro-oncology, New York University Medical Center, New York, New York 10016, United States
Charles D Stiles - Department of Microbiology and Molecular Genetics, Dana-Farber Cancer Institute, United States
Rosalind A Segal - Department of Neurology, Division of Neurosurgery, The Brain Tumor Center, Beth Israel/Deaconess Medical Center, United States
Scott L Pomeroy - Division of Neuroscience, Department of Neurology, Children 's Hospital, United States
Resource Type: Journal article
Publication Details: Cancer research (Chicago, Ill.), Vol.59(3), pp.711-719
PMID: 9973222
NLM abbreviation: Cancer Res
ISSN: 0008-5472
eISSN: 1538-7445
Publisher: American Association for Cancer Research; Philadelphia, PA
Language: English
Date published: 1999
Academic Unit: Neurology; Iowa Neuroscience Institute
Record Identifier: 9984020779502771

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