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| Status |
Public on Aug 24, 2007 |
| Title |
Dickkopf-1 is down-regulated by MYCN and inhibits neuroblastoma cell proliferation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Neuroblastomas are tumors of the developing peripheral sympathetic nervous system, which originates from the neural crest. Twenty percent of neuroblastomas show amplification of the MYCN oncogene, which correlates with poor prognosis. The MYCN transcription factor can activate and repress gene expression. To broaden our insight in the spectrum of genes down-regulated by MYCN, we generated gene expression profiles of the neuroblastoma cell lines SHEP-21N and SKNAS-NmycER, in which MYCN activity can be regulated. In this study, we show that MYCN suppresses the expression of Dickkopf-1 (DKK1) in both cell lines. DKK1 is a potent inhibitor of the wnt/beta-catenin signalling cascade, which is known to function in neural crest cell migration. We generated a DKK1 inducible cell line, IMR32-DKK1, which showed impaired proliferation upon DKK1 expression. Surprisingly, DKK1 expression did not inhibit the canonical wnt/beta-catenin signalling, suggesting a role of DKK1 in an alternative route of the wnt pathway. Gene expression profiling of two IMR32-DKK1 clones showed that only a few genes, amongst which SYNPO2, were up-regulated by DKK1. SYNPO2 encodes an actin-binding protein and was previously found to inhibit proliferation and invasiveness of prostate cancer cells. These results suggest that MYCN might stimulate cell proliferation by inhibiting the expression of DKK1. DKK1 might exert part of its growth suppressive effect by induction of SYNPO2 expression.
Keywords: DKK1, MYCN, neuroblastoma, Dickkopf
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| Overall design |
Single time course experiment, including 4 time points
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| Contributor(s) |
Koppen A, Ait-Aissa R, Hopman S, Koster J, Haneveld F, Versteeg R, Valentijn LJ |
| Citation(s) |
17643814 |
| Submission date |
Jun 08, 2007 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Linda Valentijn |
| Organization name |
Academic Medical Centre, University of Amsterdam
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| Department |
Department of Oncogenomics
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| Street address |
P.O. Box 22700
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| City |
Amsterdam |
| ZIP/Postal code |
1100DE |
| Country |
Netherlands |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (16)
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| GSM199431 |
SKNAS-NmycER, t=144 hrs |
| GSM199432 |
IMR32-DKK1 c63, t=0 |
| GSM199433 |
IMR32-DKK1 c63, t=24 hrs |
| GSM199434 |
IMR32-DKK1 c63, t=72 hrs |
| GSM199435 |
IMR32-DKK1 c63, t=288 hrs |
| GSM199436 |
IMR32-DKK1 c66, t=0 |
| GSM199437 |
IMR32-DKK1 c66, t=24 hrs |
| GSM199441 |
IMR32-DKK1 c66, t=72 hrs |
| GSM199442 |
IMR32-DKK1 c66, t=288 hrs |
| GSM199473 |
SHEP-21N, t=0 |
| GSM199474 |
SHEP-21N, t=8 hrs |
| GSM199475 |
SHEP-21N, t=24 hrs |
| GSM199479 |
SHEP-21N, t=120 hrs |
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| Relations |
| BioProject |
PRJNA100901 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE8066_RAW.tar |
202.8 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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