Expression of trkB in Human Neuroblastoma in Relation to MYCN Expression and Retinoic Acid Treatment.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/115951
- author
- 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
- organization
- publishing date
- 2003
- 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}}, }