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| Status |
Public on Feb 20, 2017 |
| Title |
Expression data from wildtype and beta-catenin activated cultured fetal mouse kidneys. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Oncogenic stabilizing mutations in the beta-catenin gene CTNNB1 are common in one class of human Wilms tumors. To model these tumors, we crossed mice carrying an inducible Cre recombinase (Rosa26-CreERT2) with a conditional gain-of-function beta-catenin allele (Ctnnb1Ex3flox). We obtained kidneys at embryonic day 13.5 and placed them in organ culture with tamoxifen. Multiple small tumors formed in the Ctnnb1∆Ex3 kidneys while the control kidneys developed normally. Immunostaining for Sall1, a marker of condensing metanephric mesenchyme, indicated that the tumors arise from this tissue compartment, analogous to the origin of human Wilms tumors. Expression profiling identified a set of induced genes overlapping with those up-regulated in human Wilms tumors with CTNNB1 mutations, including genes encoding feedback inhibitors of Wnt/beta-catenin signaling, the epithelial-mesenchymal transition (EMT) inducers, and the transcription factor E2-2 (ITF2/TCF4). A conditional deletion of E2-2 showed that this gene is important for growth of the nephroblastomas, in part via promoting an epithelial to mesenchymal transition downstream of beta-catenin. Given these cross-species validations, and genetic proof of the oncogenic function of a key downstream target gene, we expect that this rapid and efficient organ culture model will be useful for further studies to dissect and inhibit oncogenic Wnt/beta-catenin signaling.
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| Overall design |
The expression of six wildtype cultured fetal mouse kidneys was compared with six beta-catenin activated cultured fetal mouse kidneys.
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| Contributor(s) |
Yotova I, Tycko B |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Nov 18, 2014 |
| Last update date |
May 04, 2018 |
| Contact name |
Emily Hsu |
| Organization name |
Columbia University
|
| Department |
ICG
|
| Lab |
Tycko Lab
|
| Street address |
1130 St. Nicholas Ave.
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10032 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL8321 |
[Mouse430A_2] Affymetrix Mouse Genome 430A 2.0 Array |
|
| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE65899 |
Dissection of functionally relevant Wnt/beta-catenin target genes in an organ culture model of Wilms tumor |
|
| Relations |
| BioProject |
PRJNA268202 |
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