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| Status |
Public on May 09, 2016 |
| Title |
Prox1 haploinsufficiency sensitizes the pancreas to KrasG12D-induced transformation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Oncogenic mutations in Kras initiate neoplastic transformation in the pancreas through a process that hijacks the activity of developmental regulators and induces an inflammatory microenvironment. We report that the homeodomain transcription factor Prox1 is a novel component of a progenitor signature that is activated in acinar cells undergoing dedifferentiation and ductal metaplasia conversion. Also, the conditional deletion of a single Prox1 allele markedly accelerates early transformation and significantly enhances features of inflammation in pancreatic tissues carrying a Kras oncogene. By using in vitro and in silico approaches, we demonstrate that Prox1 negatively regulates the expression of proinflammatory genes and genes implicated in malignant transformation in pancreatic cells.
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| |
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| Overall design |
We used microrrays to identify gene expression profiles and pathways that are differentially activated after conditional expression of an oncogenic form of Kras and deletion of one allele of Prox1 in the pancreas
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| |
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| Contributor(s) |
Drosos Y, Neale G, Sosa-Pineda B |
| Citation(s) |
26992918 |
| |
| Submission date |
Dec 18, 2014 |
| Last update date |
Aug 06, 2018 |
| Contact name |
Geoffrey Neale |
| E-mail(s) |
geoffrey.neale@stjude.org
|
| Organization name |
St Jude Childrens Research Hospital
|
| Department |
Hartwell Center
|
| Street address |
262 Danny Thomas Place
|
| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL11180 |
[HT_MG-430_PM] Affymetrix HT MG-430 PM Array Plate |
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| Samples (9)
|
| GSM1568531 |
Pancreas with Kras activation rep1 |
| GSM1568532 |
Pancreas with Kras activation rep2 |
| GSM1568533 |
Pancreas with Kras activation rep3 |
| GSM1568534 |
Pancreas with Kras activation and Prox1 heterozygosity rep1 |
| GSM1568535 |
Pancreas with Kras activation and Prox1 heterozygosity rep2 |
| GSM1568536 |
Pancreas with Kras activation and Prox1 heterozygosity rep3 |
|
| Relations |
| BioProject |
PRJNA270747 |
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