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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 26, 2017 |
| Title |
A p53 super-tumor suppressor reveals a tumor suppressive p53-Ptpn14-Yap axis in pancreatic cancer |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The p53 transcription factor is a critical barrier to pancreatic cancer progression. To unravel mechanisms of p53-mediated tumor suppression, we analyzed pancreatic cancer predisposition in mice expressing p53 transactivation domain (TAD) mutants. Surprisingly, we observed that p53 TAD2 mutant behaves as a “super-tumor suppressor”, with an enhanced capacity to suppress pancreatic cancer and to activate a subset of novel p53 target genes. One such gene, Ptpn14, is a direct p53-inducible gene encoding a negative regulator of the Yap oncoprotein. To determine the effects of p53 deficiency on Yap target gene expression in pre-malignant mouse pancreatic intraepithelial neoplasia (PanIN) lesions, we sorted the CD133-positive ductal epithelial cells that make up the PanINs and used these cells for RNA-sequencing analysis. This analysis revealed that a Yap signature is induced upon p53 deficiency, suggesting that p53 loss promotes the induction of a Yap transcriptional program.
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| Overall design |
RNA-seq was performed to determine the differentially expressed genes in wild-type and p53-/- PanIN cells, sorted from KrasG12D;Pdx1-Cre;p53+/+ and KrasG12D;Pdx1-Cre;p53-/- mice.
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| Contributor(s) |
Mello SS, Attardi LD |
| Citation(s) |
29017057 |
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| Submission date |
Feb 06, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Stephano Spano Mello |
| Organization name |
Stanford University
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| Lab |
Attardi lab
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| Street address |
269 Campus Drive
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| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
94305 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA371474 |
| SRA |
SRP098925 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE94566_RAW.tar |
520.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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