| Project/Area Number |
10670737
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Miyazaki Medical College |
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Principal Investigator |
SUGIMOTO Tohru Miyazaki Medical College, Pediatrics, Professor, 医学部, 教授 (90117888)
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| Co-Investigator(Kenkyū-buntansha) |
KURODA Hiroshi Miyazaki Medical College, Pediatrics, Assistant Professor, 医学部, 講師 (10284837)
HORII Yoshihiro Miyazaki Medical College, Pediatrics, Assistant Professor, 医学部, 講師 (30264378)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | NEUROBLASTOMA / NEUROTROPHIC FACTORS / TRK-FAMILY RECEPTORS / SIGNAL TRANSDUCTION / GROWTH AND DIFFERENTIALTION / TRK-A受容体 / TRK-B受容体 / 細胞シグナル伝達 / 増殖 / 分化 |
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| Research Abstract |
Neuroblastoma (NB) is one of the common malignant solid tumors in childhood. TRK-family receptors (TRK-A, TRK-B and TRK-C) are the receptors for neurotrophins (NGF, BDNF, NT-3 and NT-4/5). However, little is known about the functions and signal transduction pathways of these TRK-family receptors in NBs. In this study, the signal transduction pathways and biological and clinical significance of TRK-A and TRK-B receptors in NBs were investigated and following results were obtained.
1. Signal transduction pathways through TRK-A receptors:
1) The signal, transduction of NGF was mediated to the nuclear c-fos gene in one NB cell line, whereas this transductions was blocked in three NB cell lines during their pathways.
2) In NB tumor tissues (n=24) the signal transdutions of NGF were mediated in early stage tumors(13/14 cases; 93%).
3) However the signal transdutions or NGF were less mediated in advanced stage tumors (6/10 cases; 60%).
2. Signal transduction pathways through TRK-B receptors.
1) The expressing of TRK-B is rare in NB cell lines. In this study an NB cell line, designated MP-N-TS expressing TRK-B was used.
2) In signal transduction, the tyrosine phosphorylation of a TRK-B, shc, ERK-1 and ERK-2 was increased or induced by BDNF and NT-4/5, and mediated into the nuclear c-fos gene.
3) Thus, the signal transducton of TRK-B was mediated through MAP kinase cascades and into the nuclear c-fos gene.
The signal transductions through TRK-A and TRK-B receptors can be useful to clarify the biological and clinical characteristics of patients with NB.
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