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| Status |
Public on Jan 04, 2016 |
| Title |
A designed inhibitor of p53 aggregation rescues p53 tumor-suppression in ovarian carcinomas |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Half of all human cancers lose p53 function by missense mutations, with an unknown fraction of these containing p53 in a self-aggregated, amyloid-like state. Here we show that a cell-penetrating peptide, ReACp53, designed to inhibit p53 amyloid formation, rescues p53 function in cancer cell lines and in organoids derived from high-grade serous ovarian carcinomas (HGSOC), an aggressive cancer characterized by ubiquitous p53 mutations. Rescued p53 behaves similarly to its wild-type counterpart in regulating target genes, reducing cell proliferation and increasing cell death. Intraperitoneal administration decreases tumor proliferation and shrinks xenografts in vivo. Our data show the effectiveness of targeting a specific aggregation defect of p53 and its potential applicability to HGSOCs.
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| Overall design |
Vehicle vs. ReACp53 treatment in 4 different samples: 2 cell lines (MCF7 w/ WT p53 as negative control and OVCAR3 w/ R248Q p53) and 2 clinical specimens (primary cells from patient #8 w/ WT p53 as negative control and primary cells from patient #1 w/ R248Q p53)
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| |
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| Contributor(s) |
Soragni A, Eisenberg DS, Lu J, Pellegrini M |
| Citation(s) |
26748848 |
| |
| Submission date |
Oct 30, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Sanaz Memarzadeh |
| E-mail(s) |
smemarzadeh@mednet.ucla.edu
|
| Organization name |
University of California, Los Angeles
|
| Department |
Departments of Obstetrics and Gynecology
|
| Street address |
555 Westwood Plaza
|
| City |
Los Angeles |
| State/province |
CA - California |
| ZIP/Postal code |
90095 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (24)
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| Relations |
| BioProject |
PRJNA300686 |
| SRA |
SRP065559 |
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