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Dickkopf-3 expression is a marker for neuroblastic tumor maturation and is'-down-regulated by MYCN

Koppen, Arjen; Ait-Aissa, Rachida; Koster, Jan; Øra, Ingrid LU ; Bras, Johannes; van Sluis, Peter G; Caron, Huib; Versteeg, Rogier and Valentijn, Linda J (2008) In International Journal of Cancer 122(7). p.1455-1464
Abstract
Neuroblastoma and ganglioneuroma are neuroblastic tumors originating from the developing sympathetic peripheral nervous system. Ganglioneuromas are usually benign, while neuroblastomas have a variable prognosis and include very aggressive tumors. Examples exist of neuroblastomas regressing to ganglioneuromas and ganglioneuromas progressing to neuroblastomas. Little is known of the molecular differences between the tumor types. Here we report that Dickkopf-3 (DKK3), a putative extra cellular inhibitor of the Wnt/beta-catenin pathway, showed a strongly differential expression between neuroblastoma and ganglioneuroma. Microarray analyses of 109 neuroblastic tumors revealed that DKK3 is strongly expressed in ganglioneuroma but only weakly in... (More)
Neuroblastoma and ganglioneuroma are neuroblastic tumors originating from the developing sympathetic peripheral nervous system. Ganglioneuromas are usually benign, while neuroblastomas have a variable prognosis and include very aggressive tumors. Examples exist of neuroblastomas regressing to ganglioneuromas and ganglioneuromas progressing to neuroblastomas. Little is known of the molecular differences between the tumor types. Here we report that Dickkopf-3 (DKK3), a putative extra cellular inhibitor of the Wnt/beta-catenin pathway, showed a strongly differential expression between neuroblastoma and ganglioneuroma. Microarray analyses of 109 neuroblastic tumors revealed that DKK3 is strongly expressed in ganglioneuroma but only weakly in neuroblastoma. Low DKK3 expression in neuroblastoma correlated with a poor prognosis. The expression of DKK3 in the tumor series and in neuroblastoma cell lines was inversely correlated with the expression of the MYCN oncogene. Analysis of, 2 neuroblastoma cell lines with inducible activity of MYCN showed that DKK3 is down-regulated by MYCN. We subsequently generated cell lines with inducible expression of DKK3, which revealed an inhibitory effect of DKK3 on proliferation. High DKK3 expression in the benign ganglioneuromas and down-regulation of DKK3 by MYCN in neuroblastoma might contribute to the strongly different clinical behavior of both neuroblastic tumor types. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ganglioneuroma, neuroblastoma, neuroblastic, DKK3, MYCN
in
International Journal of Cancer
volume
122
issue
7
pages
1455 - 1464
publisher
John Wiley & Sons
external identifiers
  • wos:000253441100002
  • scopus:39649085571
ISSN
0020-7136
DOI
10.1002/ijc.23180
language
English
LU publication?
yes
id
c826638a-593a-4286-8d50-9e798d9bc9fa (old id 1193760)
date added to LUP
2008-09-09 10:25:27
date last changed
2017-04-23 03:28:31
@article{c826638a-593a-4286-8d50-9e798d9bc9fa,
  abstract     = {Neuroblastoma and ganglioneuroma are neuroblastic tumors originating from the developing sympathetic peripheral nervous system. Ganglioneuromas are usually benign, while neuroblastomas have a variable prognosis and include very aggressive tumors. Examples exist of neuroblastomas regressing to ganglioneuromas and ganglioneuromas progressing to neuroblastomas. Little is known of the molecular differences between the tumor types. Here we report that Dickkopf-3 (DKK3), a putative extra cellular inhibitor of the Wnt/beta-catenin pathway, showed a strongly differential expression between neuroblastoma and ganglioneuroma. Microarray analyses of 109 neuroblastic tumors revealed that DKK3 is strongly expressed in ganglioneuroma but only weakly in neuroblastoma. Low DKK3 expression in neuroblastoma correlated with a poor prognosis. The expression of DKK3 in the tumor series and in neuroblastoma cell lines was inversely correlated with the expression of the MYCN oncogene. Analysis of, 2 neuroblastoma cell lines with inducible activity of MYCN showed that DKK3 is down-regulated by MYCN. We subsequently generated cell lines with inducible expression of DKK3, which revealed an inhibitory effect of DKK3 on proliferation. High DKK3 expression in the benign ganglioneuromas and down-regulation of DKK3 by MYCN in neuroblastoma might contribute to the strongly different clinical behavior of both neuroblastic tumor types.},
  author       = {Koppen, Arjen and Ait-Aissa, Rachida and Koster, Jan and Øra, Ingrid and Bras, Johannes and van Sluis, Peter G and Caron, Huib and Versteeg, Rogier and Valentijn, Linda J},
  issn         = {0020-7136},
  keyword      = {ganglioneuroma,neuroblastoma,neuroblastic,DKK3,MYCN},
  language     = {eng},
  number       = {7},
  pages        = {1455--1464},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Dickkopf-3 expression is a marker for neuroblastic tumor maturation and is'-down-regulated by MYCN},
  url          = {http://dx.doi.org/10.1002/ijc.23180},
  volume       = {122},
  year         = {2008},
}