PMID- 11223544
OWN - NLM
STAT- MEDLINE
DCOM- 20010517
LR  - 20190513
IS  - 0910-5050 (Print)
IS  - 1876-4673 (Electronic)
IS  - 0910-5050 (Linking)
VI  - 92
IP  - 2
DP  - 2001 Feb
TI  - Signal transduction pathways through TRK-A and TRK-B receptors in human 
      neuroblastoma cells.
PG  - 152-60
AB  - Little is known about the signal transduction pathways of TRK family receptors in 
      neuroblastoma (NB) cells. In this study, an NB cell line, designated MP-N-TS, was 
      established from an adrenal tumor taken from a 2-year-old boy. This cell line 
      expressed both TRK-A and TRK-B receptors, which is rare in a single NB cell line. 
      Therefore, the MP-N-TS cell line was used to determine whether the signal 
      transduction through these constitutive receptors is functional. Three 
      neurotrophins, nerve growth factor (NGF), brain-derived neurotrophic factor 
      (BDNF) and neurotrophin-4 / 5 (NT-4 / 5), induced tyrosine phosphorylation of 
      panTRK, and BDNF and NT-4 / 5 induced tyrosine phosphorylation of TRK-B. Tyrosine 
      phosphorylation of panTRK and / or TRK-B by the neurotrophins was inhibited in 
      the presence of a tyrosine kinase inhibitor K252a. Tyrosine phosphorylation of 
      Src homologous and collagen (Shc), extracellular signal-regulated kinase (ERK)-1 
      and ERK-2, and phospholipase C-gamma1 (PLC-gamma1) was increased by the three 
      neurotrophins and the increase was inhibited in the presence of K252a. Activation 
      of Ras, detected as the GTP-bound form of Ras, was induced by the three 
      neurotrophins. The neurotrophins did not modulate the expressions of TRK-A or 
      TRK-B mRNA, but they did induce the expression of c-fos mRNA. Exogenous NGF 
      induced weak neurite outgrowth, whereas exogenous BDNF and NT-4 / 5 induced 
      distinct neurite outgrowth. Exogenous BDNF and NT-4 / 5 increased the number of 
      viable cells, while NGF did not. Our results demonstrate that the signal 
      transduction pathways through TRK-A and TRK-B in MP-N-TS cells are functional and 
      similar, and the main downstream signaling pathways from the three neurotrophins 
      are mitogen-activated protein kinase (MAPK) cascades through Shc, activated Ras, 
      ERK-1 and ERK-2, and the transduction pathway through PLC-gamma1. Further, BDNF 
      and NT-4 / 5 increased cell viability. The MP-N-TS cell line should be useful for 
      clarifying the TRK-A and TRK-B signaling pathways responsible for the different 
      prognoses in patients with NB.
FAU - Sugimoto, T
AU  - Sugimoto T
AD  - Department of Pediatrics, Kyoto Prefectural University of Medicine, Hirokoji, 
      Kawaramachi, Kamigyo-ku, Kyoto 602-8566, Japan. tosugimo@koto.kpu-m.ac.jp
FAU - Kuroda, H
AU  - Kuroda H
FAU - Horii, Y
AU  - Horii Y
FAU - Moritake, H
AU  - Moritake H
FAU - Tanaka, T
AU  - Tanaka T
FAU - Hattori, S
AU  - Hattori S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Jpn J Cancer Res
JT  - Japanese journal of cancer research : Gann
JID - 8509412
RN  - 0 (Carbazoles)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indole Alkaloids)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (RNA, Messenger)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - 97161-97-2 (staurosporine aglycone)
RN  - EC 2.7.10.1 (Receptor, trkA)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.6.5.2 (HRAS protein, human)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
SB  - IM
MH  - Adrenal Gland Neoplasms/genetics/metabolism/pathology
MH  - Animals
MH  - Carbazoles/pharmacology
MH  - Cell Differentiation
MH  - Cell Survival
MH  - Child, Preschool
MH  - Enzyme Inhibitors/pharmacology
MH  - Humans
MH  - Indole Alkaloids
MH  - Kinetics
MH  - Male
MH  - Nerve Growth Factors/pharmacology
MH  - Neuroblastoma/genetics/*metabolism/pathology
MH  - PC12 Cells
MH  - Phosphorylation
MH  - Phosphotyrosine/metabolism
MH  - Proto-Oncogene Proteins c-fos/biosynthesis/genetics
MH  - Proto-Oncogene Proteins p21(ras)/metabolism
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Receptor, trkA/genetics/*metabolism
MH  - Receptor, trkB/genetics/*metabolism
MH  - *Signal Transduction
MH  - Tumor Cells, Cultured
PMC - PMC5926689
EDAT- 2001/02/27 10:00
MHDA- 2001/05/18 10:01
PMCR- 2001/02/01
CRDT- 2001/02/27 10:00
PHST- 2001/02/27 10:00 [pubmed]
PHST- 2001/05/18 10:01 [medline]
PHST- 2001/02/27 10:00 [entrez]
PHST- 2001/02/01 00:00 [pmc-release]
AID - CAE152 [pii]
AID - 10.1111/j.1349-7006.2001.tb01077.x [doi]
PST - ppublish
SO  - Jpn J Cancer Res. 2001 Feb;92(2):152-60. doi: 10.1111/j.1349-7006.2001.tb01077.x.