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Expression of trkB in Human Neuroblastoma in Relation to MYCN Expression and Retinoic Acid Treatment.

Edsjö, Anders LU ; Lavenius, Erik ; Nilsson, Helén LU ; Hoehner, Jeff C ; Simonsson, Per LU ; Culp, Lloyd A ; Martinsson, Tommy ; Larsson, Christer LU and Påhlman, Sven LU (2003) In Laboratory Investigation 83(6). p.813-823
Abstract
Expression of full-length trkB can be found in some highly malignant neuroblastoma tumors with an amplified MYCN gene. This contrasts sympathetic neuroblasts, from which neuroblastomas are thought to arise, which neither express trkB nor are dependent on the p145trkB ligands, brain-derived neurotrophic factor (BDNF) or neurotrophin-4/5, for their normal development. In this study we show that trkB was expressed in two out of five neuroblastoma tumors with amplified MYCN, while no trkB expression was observed when the MYCN gene was overexpressed in a non–MYCN-amplified neuroblastoma cell line. This shows that MYCN overexpression per se is not sufficient to induce trkB expression. trkB expression and BDNF responsiveness in neuroblastoma... (More)
Expression of full-length trkB can be found in some highly malignant neuroblastoma tumors with an amplified MYCN gene. This contrasts sympathetic neuroblasts, from which neuroblastomas are thought to arise, which neither express trkB nor are dependent on the p145trkB ligands, brain-derived neurotrophic factor (BDNF) or neurotrophin-4/5, for their normal development. In this study we show that trkB was expressed in two out of five neuroblastoma tumors with amplified MYCN, while no trkB expression was observed when the MYCN gene was overexpressed in a non–MYCN-amplified neuroblastoma cell line. This shows that MYCN overexpression per se is not sufficient to induce trkB expression. trkB expression and BDNF responsiveness in neuroblastoma cells can be induced by all-trans-retinoic acid (RA). When SH-SY5Y cells were stimulated with a combination of RA and BDNF, norepinephrine and tyrosine hydroxylase levels were unaltered, showing that the cells did not change toward a more catecholaminergic sympathetic phenotype. However, expression of growth-associated protein 43, indicative of a neuronal phenotype, was elevated. Vesicular acetylcholine transporter, choline acetyl transferase, and neuropeptide tyrosine mRNA levels also increased in RA-BDNF–treated cells, which could suggest that these cells develop into a sympathetic cholinergic phenotype. In addition, treatment with RA-induced expression of the platelet-derived growth factor receptor-alpha. As previously shown for BDNF, platelet-derived growth factor stimulated growth of the RA-treated cells, findings that could have clinical relevance. If these receptors mediate a mitogenic signal in vivo also, this might limit the effect of RA treatment on neuroblastoma patients. (Less)
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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Laboratory Investigation
volume
83
issue
6
pages
813 - 823
publisher
Nature Publishing Group
external identifiers
  • wos:000183718700005
  • scopus:0038340662
ISSN
1530-0307
DOI
10.1097/01.LAB.0000074895.48776.D8
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Tumour Cell Biology (013017530), Clinical Chemistry, Malmö (013016000), Molecular Medicine (013031200)
id
e02dd02a-e56a-4c9e-9122-ce2462d01b2f (old id 115951)
alternative location
http://www.nature.com/labinvest/journal/v83/n6/abs/3780668a.html
date added to LUP
2016-04-01 11:34:57
date last changed
2022-03-28 00:09:20
@article{e02dd02a-e56a-4c9e-9122-ce2462d01b2f,
  abstract     = {{Expression of full-length trkB can be found in some highly malignant neuroblastoma tumors with an amplified MYCN gene. This contrasts sympathetic neuroblasts, from which neuroblastomas are thought to arise, which neither express trkB nor are dependent on the p145trkB ligands, brain-derived neurotrophic factor (BDNF) or neurotrophin-4/5, for their normal development. In this study we show that trkB was expressed in two out of five neuroblastoma tumors with amplified MYCN, while no trkB expression was observed when the MYCN gene was overexpressed in a non–MYCN-amplified neuroblastoma cell line. This shows that MYCN overexpression per se is not sufficient to induce trkB expression. trkB expression and BDNF responsiveness in neuroblastoma cells can be induced by all-trans-retinoic acid (RA). When SH-SY5Y cells were stimulated with a combination of RA and BDNF, norepinephrine and tyrosine hydroxylase levels were unaltered, showing that the cells did not change toward a more catecholaminergic sympathetic phenotype. However, expression of growth-associated protein 43, indicative of a neuronal phenotype, was elevated. Vesicular acetylcholine transporter, choline acetyl transferase, and neuropeptide tyrosine mRNA levels also increased in RA-BDNF–treated cells, which could suggest that these cells develop into a sympathetic cholinergic phenotype. In addition, treatment with RA-induced expression of the platelet-derived growth factor receptor-alpha. As previously shown for BDNF, platelet-derived growth factor stimulated growth of the RA-treated cells, findings that could have clinical relevance. If these receptors mediate a mitogenic signal in vivo also, this might limit the effect of RA treatment on neuroblastoma patients.}},
  author       = {{Edsjö, Anders and Lavenius, Erik and Nilsson, Helén and Hoehner, Jeff C and Simonsson, Per and Culp, Lloyd A and Martinsson, Tommy and Larsson, Christer and Påhlman, Sven}},
  issn         = {{1530-0307}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{813--823}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Laboratory Investigation}},
  title        = {{Expression of trkB in Human Neuroblastoma in Relation to MYCN Expression and Retinoic Acid Treatment.}},
  url          = {{http://dx.doi.org/10.1097/01.LAB.0000074895.48776.D8}},
  doi          = {{10.1097/01.LAB.0000074895.48776.D8}},
  volume       = {{83}},
  year         = {{2003}},
}