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Therapeutic Targeting of BET Bromodomain Proteins in Castration-Resistant Prostate Cancer (microarray)

GSE55063 Homo sapiens (human) Expression microarray 48 samples Submitted 2014/04/25 Platform GPL4133
At a glance

Expression microarray · human · 48 samples

What it is
Expression microarrayGene activity read on a chip (the older technology that RNA-seq replaced).
Organism
Homo sapiens (human)
Samples
48 samples
Data you can get
A processed expression table (series matrix) and the array files, from NCBI.
Summary (written by the submitters)
Men who develop metastatic castration-resistant prostate cancer (CRPC) invariably succumb to the disease. The development and progression to CRPC following androgen ablation therapy is predominantly driven by unregulated androgen receptor (AR) signaling1-3. Despite the success of recently approved therapies targeting AR signaling such as abiraterone4-6 and second generation anti-androgens MDV3100 (enzalutamide)7,8, durable responses are limited, presumably due to acquired resistance.
Read the full summary ↓
Recently JQ1 and I-BET, two selective small molecule inhibitors that target the amino-terminal bromodomains of BRD4, have been shown to exhibit antiproliferative effects in a range of malignancies9-12. Here we show that AR signaling-competent CRPC cell lines are preferentially sensitive to BET bromodomain inhibition. BRD4 physically interacts with the N-terminal domain of AR and can be disrupted by JQ111,13. Like the direct AR antagonist, MDV3100, JQ1 disrupted AR recruitment to target gene loci. In contrast to MDV3100, JQ1 functions downstream of AR, and more potently abrogated BRD4 localization to AR target loci and AR mediated gene transcription including induction of TMPRSS2-ERG and its oncogenic activity. In vivo, BET bromodomain inhibition was more efficacious than direct AR antagonism in CRPC xenograft models. Taken together, these studies provide a novel epigenetic approach for the concerted blockade of oncogenic drivers in advanced prostate cancer.
This dataset
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Download · which file do I need?

Direct links to NCBI, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need.

All supplementary files ↗
3 · The original raw files

Whole study · RAW.tar

Everything the authors deposited as one archive (GSE55063_RAW.tar), including the raw array or instrument files. Can be large; the picker in step 2 takes just the samples you need.

Whole study · RAW.tar ↓

What the files usually look like: For arrays the series matrix is normally the normalised expression table you want; the raw array files (CEL and similar) are in the RAW.tar.

Also filed as BioProject PRJNA238360. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 24759320) ↗
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