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| Status |
Public on Sep 20, 2021 |
| Title |
Transcriptomic effect of retroviral overexpression of PIK3CA-H1047R in breast epithelial MCF10A cells; +/- 500 nM BYL719 as a function of time (48h and 120h). |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The aim of this experiment was to evaluate the transcriptomic effects of PI3K pathway hyperactivation vs inhibition, in the context of PIK3CA-H1047R overexpression in MCF10A breast epithelial cells. The cells were processed for RNA sequencing, with the t values from subsequent differential gene expression processing used for gene set enrichment analysis (GSEA) with the MSigDB HALLMARK_PI3K_AKT_MTOR_SIGNALING gene signature. We demonstrate that the HALLMARK_PI3K_AKT_MTOR_SIGNALING gene signature can be used as a transcriptional footprint of PI3K pathway activation: it correctly predicts activation of the pathway in DMSO-treated PIK3CA-H1047R MCF10A cells relative to EV controls; conversely, it also correctly predicts pathway inhibition upon p110 inhibition with BYL719.
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| Overall design |
Transcriptomic data from untransformed, immortalised human breast epithelial MCF10A cells with retrovirally-mediated overexpression of the PIK3CA-H1047R oncogene, alongside the respective empty vector (EV) control cells; assessed in growth factor-replete conditions, with PIK3CA-H1047R also exposed to either DMSO or 500 nM BYL719 (p110alpha-specific inhibitor) in order to determine the extent to which the transcriptomic phenotype can be reversed. Data were obtained from two treatment time points - 48h and 120h. Following differential gene expression analysies with limma-voom, the genes were ranked according to the t values specifying a given comparison, and used to determine whether conventional gene set enrichment analysis (GSEA) with the the mSigDb "HALLMARK_PI3K_AKT_MTORC1" gene signature would distinguish samples with PI3K pathway activation vs inhibition.
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| Contributor(s) |
Madsen RR, Toker A, Erickson EC |
| Citation(s) |
34762647 |
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| Submission date |
Sep 16, 2021 |
| Last update date |
Nov 19, 2021 |
| Contact name |
Ralitsa Radostinova Madsen |
| E-mail(s) |
rmadsen001@dundee.ac.uk
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| Organization name |
School of Life Sciences, University of Dundee
|
| Department |
Medical Research Council Protein Phosphorylation and Ubiquitylation Unit
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| Lab |
Madsen Lab
|
| Street address |
Dow Street
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| City |
Dundee |
| ZIP/Postal code |
DD1 5EH |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA763878 |
| SRA |
SRP337420 |
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