Dickkopf-1 is down-regulated by MYCN and inhibits neuroblastoma cell proliferation
From ArrayWiki
| PubMed ID: | 17643814 |
|---|---|
| Contact: | Rogier Versteeg
|
| Species: | Homo sapiens |
| Platform: | Affymetrix GeneChip Human Genome U133 Plus 2.0 Array |
| Number of Samples: | 16 |
| Date Range: | 11/02/2004 - 05/31/2005 |
| Experiment Quality: | 87.86 0.19 % |
| Link to Repository: | GSE8066 |
| Original Intensity Data: | Download |
| Clean Intensity Data: | Download |
| Original PLIER Data: | Download |
| Clean PLIER Data: | Download |
| Clean CEL Files: | |
| Data Rank: | 
|
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/-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/-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.
Design: Single time course experiment, including 4 time points
Type: DKK1, MYCN, neuroblastoma, Dickkopf
Contents |
[edit] Contributors
- Arjen Koppen
- Rachida Ait-Aissa
- Saskia Hopman
- Jan Koster
- Franciska Haneveld
- Rogier Versteeg
- Linda J Valentijn
[edit] Protocols
[edit] References
[edit] Links
GEO Accession for this experiment: GSE8066. (Public on Aug 24 2007)
PubMed abstract: 17643814
RAW data: tar file.
[edit] Analysis
 Before Normalization |
 After Normalization & Cleaning |
[edit] Samples/Quality Control
| Sample | Date Scanned | Source Link | Probe Variance Data | Artifact Mask | Quality Score |
|---|---|---|---|---|---|
| SKNAS-NmycER, t=0 | 05/31/05 10:36:58 | GSM199428 | 
| 
| 77.6698 0.38 % |
| SKNAS-NmycER, t=24 hrs | 05/31/05 11:08:14 | GSM199429 | 
| 
| 81.9931 0.15 % |
| SKNAS-NmycER, t=72 hrs | 05/31/05 11:30:38 | GSM199430 | 
| 
| 85.616 0.68 % |
| SKNAS-NmycER, t=144 hrs | 05/31/05 11:43:50 | GSM199431 | 
| 
| 85.2611 0.26 % |
| IMR32-DKK1 c63, t=0 | 02/16/05 12:32:41 | GSM199432 | 
| 
| 84.8737 0.35 % |
| IMR32-DKK1 c63, t=24 hrs | 02/16/05 14:17:39 | GSM199433 | 
| 
| 87.6764 0.02 % |
| IMR32-DKK1 c63, t=72 hrs | 02/16/05 14:34:09 | GSM199434 | 
| 
| 92.7512 0.02 % |
| IMR32-DKK1 c63, t=288 hrs | 02/16/05 14:47:08 | GSM199435 | 
| 
| 91.5381 0 % |
| IMR32-DKK1 c66, t=0 | 02/16/05 15:00:02 | GSM199436 | 
| 
| 89.3134 0.37 % |
| IMR32-DKK1 c66, t=24 hrs | 02/15/05 12:56:36 | GSM199437 | 
| 
| 90.2871 0.03 % |
| IMR32-DKK1 c66, t=72 hrs | 02/15/05 13:19:23 | GSM199441 | 
| 
| 88.6938 0.02 % |
| IMR32-DKK1 c66, t=288 hrs | 02/15/05 13:58:41 | GSM199442 | 
| 
| 89.7589 0.01 % |
| SHEP-21N, t=0 | 11/02/04 12:58:53 | GSM199473 | 
| 
| 88.3101 0.34 % |
| SHEP-21N, t=8 hrs | 11/02/04 13:16:57 | GSM199474 | 
| 
| 90.1625 0.32 % |
| SHEP-21N, t=24 hrs | 11/02/04 13:38:40 | GSM199475 | 
| 
| 91.0162 0.01 % |
| SHEP-21N, t=120 hrs | 11/02/04 13:54:28 | GSM199479 | 
| 
| 90.7667 0.12 % |
