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Expression profiling of MCF7 cells upon nutlin3a treatment

ABSTRACT: The tumor suppressor p53 can induce various biological responses. Yet it is not clear whether it is p53 in vivo promoter selectivity that triggers different transcription programs leading to different outcomes. Our analysis of genome-wide chromatin occupancy by p53 using ChIP-seq (deposited in Sequence Read Archive database as SRP007261) revealed “p53 default program”, i.e. the pattern of major p53-bound sites that is similar upon p53 activation by nutlin3a, RITA or 5-FU in breast cancer cells, despite different biological outcomes triggered by these compounds. Parallel analysis of gene expression allowed identification of 280 previously unknown p53 target genes, including p53-repressed AURKA. The consensus p53 binding motif was present more frequently in p53-induced, than in repressed targets, indicating different mechanisms of gene activation versus repression. We identified several possible cofactors of p53, and found that STAT3 antagonised p53-mediated repression of a subset of genes, including AURKA. Finally, we showed that the expression of the novel p53 targets correlates with p53 status and survival in breast cancer patients. We used microarrays to detail the global programme of gene expression changed upon nutlin3a treatment and knocking-down of STAT3 transcription program MCF7 cell with or without knock-down of STAT3 were treated with nutlin3a and collected for RNA extraction and hybridization on Affymetrix microarrays.

ORGANISM(S): Homo sapiens

SUBMITTER: Nikulenkov F

PROVIDER: S-ECPF-GEOD-30183 | biostudies-other | 2012 Dec

REPOSITORIES: biostudies-other

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