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E-GEOD-11578 - Effect of wtp53-reactivating drug RITA on HCT116 cells

Status
Released on 28 February 2009, last updated on 27 March 2012
Organism
Homo sapiens
Samples (12)
Array (1)
Protocols (7)
Description
Since its discovery as a tumour suppressor some fifteen years ago, the transcription factor p53 has attracted paramount attention for its role as “the guardian of the genome”. TP53 mutations occur so frequently in cancer, regardless of patient age or tumour type, that they appear to be part of the life history of at least 50% of human tumours. In most tumours that retain wild-type p53, its function is inactivated due to deregulated HDM2, a protein which binds to p53 and which can inhibit the transcriptional activity of p53 and induce its degradation. RITA is a low-molecular-weight compound which addresses the second group of tumours retaining functionally reactive wt p53. It was found in a screening of the National Cancer Institute (NCI) library of low-molecular-weight compounds based on its ability to selectively kill wtp53-containing cells. RITA binds directly to p53 and diplaces its main destructor Mdm2, as well as inducing a shift in the conformation of p53. This is in contrast to the wtp53-reactivating compound Nutlin3a, which targets Mdm2, inhibiting its ability to degrade p53. Using microarray technology we have explored the effect of RITA on the transcriptome of isogenic cell-lines with knocked-out (KO) or intact (WT) TP53. While the effects on KO cells are below detection limit, the effects on WT cells are profound. The known p53 targets induced are predominately apoptotic, in contrast to the genes affected by Nutlin3a, which are exclusively growth-arrest genes. Keywords: Antitumor agent HCT116 parental and HCT116 p53-null (HCT116 TP53-/-) cells were subjected to treatment with 1uM RITA for 12h, or left untreated. The experiment was done in three independent biological replicates.
Experiment type
transcription profiling by array 
Contacts
Martin Enge
Citation
Ablation of key oncogenic pathways by RITA-reactivated p53 is required for efficient apoptosis. Grinkevich VV, Nikulenkov F, Shi Y, Enge M, Bao W, Maljukova A, Gluch A, Kel A, Sangfelt O, Selivanova G. , PMID:19411072
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-11578.idf.txt
Sample and data relationshipE-GEOD-11578.sdrf.txt
Raw data (1)E-GEOD-11578.raw.1.zip
Processed data (1)E-GEOD-11578.processed.1.zip
Experiment designE-GEOD-11578.biosamples.png, E-GEOD-11578.biosamples.svg
Array designA-AFFY-37.adf.txt
R ExpressionSetE-GEOD-11578.eSet.r
Links