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Series GSE11578 Query DataSets for GSE11578
Status Public on Feb 28, 2009
Title Effect of wtp53-reactivating drug RITA on HCT116 cells
Organism Homo sapiens
Experiment type Expression profiling by array
Summary 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
Overall design 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.
Contributor(s) Enge M
Citation(s) 19411072, 19249676
Submission date May 28, 2008
Last update date Dec 06, 2018
Contact name Martin Enge
Organization name Karolinska Institute
Department Dep of Oncology-Pathology
Street address CCK, Z4
City Stockholm
ZIP/Postal code S-171 76
Country Sweden
Platforms (1)
GPL571 [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array
Samples (12)
GSM291526 null.untr.1
GSM291527 null.untr.2
GSM291528 null.untr.3
BioProject PRJNA106207

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Supplementary file Size Download File type/resource
GSE11578_RAW.tar 24.4 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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