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Status |
Public on May 12, 2009 |
Title |
MCF7 time-series upon RITA treatment. |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Targeting “oncogene addiction” is a promising strategy for anti-cancer therapy. Here, we report a potent inhibition of crucial oncogenes by p53 upon reactivation with small molecule RITA in vitro and in vivo. RITA-activated p53 unleashes transcriptional repression of anti-apoptotic proteins Mcl-1, Bcl-2, MAP4, and survivin, blocks Akt pathway on several levels and downregulates c-Myc, cyclin E and B-catenin. p53 ablates c-Myc expression via several mechanisms at transcriptional and posttranscriptional level. We show that transrepression of oncogenes correlated with higher level of p53 bound to chromatin-bound p53 than transactivation of pro-apoptotic targets. Inhibition of oncogenes by p53 reduces the cell’s ability to buffer pro-apoptotic signals and elicits robust apoptosis. Our study highlights the role of transcriptional repression for p53-mediated tumor suppression.
Keywords: time course
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Overall design |
Breast carcinoma cell-line MCF7 was treated with the small-molecule p53 activator RITA for 2h, 8h, 16h and 24h.
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Contributor(s) |
Enge M, Gluch A |
Citation(s) |
19411072 |
Submission date |
Oct 21, 2008 |
Last update date |
Dec 06, 2018 |
Contact name |
Martin Enge |
E-mail(s) |
martin.enge@ki.se
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Organization name |
Karolinska Institute
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Department |
Dep of Oncology-Pathology
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Street address |
CCK, Z4
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City |
Stockholm |
ZIP/Postal code |
S-171 76 |
Country |
Sweden |
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Platforms (1) |
GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
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Samples (5)
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Relations |
BioProject |
PRJNA109617 |
Supplementary file |
Size |
Download |
File type/resource |
GSE13291_RAW.tar |
9.3 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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