PMID- 8264643
OWN - NLM
STAT- MEDLINE
DCOM- 19940121
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 14
IP  - 1
DP  - 1994 Jan
TI  - Expression and function of TRK-B and BDNF in human neuroblastomas.
PG  - 759-67
AB  - There is considerable interest in the role of the TRK family of neuotrophin 
      receptors in regulating growth and differentiation in normal and neoplastic nerve 
      cells. A neuroblastoma is a common pediatric tumor derived from the neural crest, 
      and the majority of favorable neuroblastomas express a high level of TRK-A mRNA. 
      However, little is known about the expression or function of TRK-B in these 
      tumors. TRK-B encodes a tyrosine kinase that binds to brain-derived neuotrophic 
      factor (BDNF), as well as neurotrophin-3 (NT-3) and NT-4/5. We have studied the 
      N-myc-amplified human neuroblastoma cell line, SMS-KCN, which expresses both 
      TRK-B and BDNF. Exogenous BDNF induces tyrosine phosphorylation of TRK-B as well 
      as phosphorylation of phospholipase C-gamma 1, the extracellular signal-regulated 
      kinases 1 and 2, and phosphatidylinositol-3 kinase. BDNF also induces expression 
      of the immediate-early genes c-FOS and NGFI-A but not NGFI-B or NGFI-C. In 
      addition, BDNF appears to promote cell survival and neurite outgrowth. SMS-KCN 
      cells also express TRK-A, which is phosphorylated in response to nerve growth 
      factor. However, the downstream TRK-A signaling is apparently defective. Finally, 
      we determined that in a series of 74 primary neuroblastomas, 36% express TRK-B 
      mRNA, 68% express BDNF mRNA, and 31% express both. Truncated TRK-B appears to be 
      preferentially expressed in more-differentiated tumors (ganglioneuromas and 
      ganglioneuroblastomas), whereas full-length TRK-B is expressed almost exclusively 
      in immature neuroblastomas with N-myc amplification. Our findings suggest that in 
      TRK-B-expressing human neuroblastomas, BDNF promotes survival and induces neurite 
      outgrowth in an autocrine or paracrine manner. The BDNF/TRK-B pathway may be 
      particularly important for growth and differentiation of neuroblastomas with 
      N-myc amplification.
FAU - Nakagawara, A
AU  - Nakagawara A
AD  - Department of Pediatrics, Washington University School of Medicine, St. Louis, 
      Missouri 63110.
FAU - Azar, C G
AU  - Azar CG
FAU - Scavarda, N J
AU  - Scavarda NJ
FAU - Brodeur, G M
AU  - Brodeur GM
LA  - eng
GR  - CA-39771/CA/NCI NIH HHS/United States
GR  - CA-49712/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (Receptor, Ciliary Neurotrophic Factor)
RN  - 0 (Receptors, Growth Factor)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, trkA)
SB  - IM
GS  - BDNF
GS  - LNGFR
GS  - N-myc
GS  - NGF
GS  - TRK-A
GS  - TRK-B
MH  - Brain-Derived Neurotrophic Factor
MH  - Cell Differentiation/drug effects/genetics
MH  - Cell Division/drug effects
MH  - Child
MH  - Gene Expression
MH  - Gene Expression Regulation, Neoplastic
MH  - Genes, myc
MH  - Humans
MH  - Neoplasm Proteins/metabolism
MH  - Nerve Tissue Proteins/*genetics/metabolism/pharmacology
MH  - Neuroblastoma/*genetics/*metabolism/pathology
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins/genetics/metabolism
MH  - RNA, Messenger/genetics
MH  - RNA, Neoplasm/genetics
MH  - Receptor Protein-Tyrosine Kinases/genetics/metabolism
MH  - Receptor, Ciliary Neurotrophic Factor
MH  - Receptor, trkA
MH  - Receptors, Growth Factor/*genetics/metabolism
MH  - Receptors, Nerve Growth Factor/genetics/metabolism
MH  - Signal Transduction
MH  - Tumor Cells, Cultured/drug effects/metabolism/pathology
PMC - PMC358424
EDAT- 1994/01/01 00:00
MHDA- 1994/01/01 00:01
PMCR- 1994/01/01
CRDT- 1994/01/01 00:00
PHST- 1994/01/01 00:00 [pubmed]
PHST- 1994/01/01 00:01 [medline]
PHST- 1994/01/01 00:00 [entrez]
PHST- 1994/01/01 00:00 [pmc-release]
AID - 10.1128/mcb.14.1.759-767.1994 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1994 Jan;14(1):759-67. doi: 10.1128/mcb.14.1.759-767.1994.