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GEO help: Mouse over screen elements for information. |
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| Status |
Public on May 22, 2013 |
| Title |
TH-MYCN Mice with Caspase-8 Deficiency Develop Advanced Neuroblastoma with Bone Marrow Metastasis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Neuroblastoma, the most common extracranial pediatric solid tumor, is responsible for 15% of all childhood cancer deaths. Patients frequently present at diagnosis with metastatic disease, particularly to the bone marrow. Advances in therapy and understanding of the metastatic process have been limited due in part, to the lack of animal models harboring bone marrow disease. The widely employed transgenic model, the TH-MYCN mouse, exhibits limited metastasis to this site. Here we establish the first genetic immunocompetent mouse model for metastatic neuroblastoma with enhanced secondary tumors in the bone marrow. This model recapitulates two frequent alterations in metastatic neuroblasoma, over-expression of MYCN and loss of caspase-8 expression. In this model, the mouse caspase-8 gene was deleted in neural crest lineage cells by crossing a TH-Cre transgenic mouse with a caspase-8 conditional knockout mouse. This mouse was then crossed with the neuroblastoma prone TH-MYCN mouse. While over-expression of MYCN by itself rarely caused bone marrow metastasis (5% average incidence), combining MYCN overexpression and caspase-8 deletion significantly increased bone marrow metastasis (37% average incidence). Loss of caspase-8 expression did not alter the site, incidence, or latency of the primary tumors. However, secondary tumors were detected in the bone marrow of these mice as early as week 9-10. The mouse model described in this work is a valuable tool to enhance our understanding of metastatic neuroblastoma and treatment options and underscores the role of caspase-8 in neuroblastoma progression.
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| Overall design |
Survey of spontateous 24 NB tumors and 5 bone marrow samples in wt and transgenic mice.
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| Contributor(s) |
Teitz T, Inoue M, Valentine MB, Zhu K, Rehg JE, Zhao W, Finkelstein D, Wang Y, Johnson MD, Calabrese C, Rubinstein M, Hakem R, Weiss WA, Lahti JM |
| Citation(s) |
23536557 |
| Submission date |
Nov 27, 2012 |
| Last update date |
Feb 11, 2019 |
| Contact name |
David Finkelstein |
| E-mail(s) |
david.finkelstein@stjude.org
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| Phone |
9014953931
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| Organization name |
St Jude Children's Research Hospital
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| Department |
Computational Biology
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| Street address |
332 N. Lauderdale St.
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| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (29)
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| Relations |
| BioProject |
PRJNA182245 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE42548_RAW.tar |
97.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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