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5β-Dihydrotestosterone and mutant androgen receptor vulnerability in prostate cancer

GSE339459 Homo sapiens (human) RNA-seq (gene expression) 30 samples Submitted 2026/08/08 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 30 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Topic
Prostate cancerThis series is part of our curated briefing on it.
Samples
30 samples: 10 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Summary (written by the submitters)
BACKGROUND Bipolar androgen therapy (BAT) exploits the paradoxical vulnerability of castration-resistant prostate cancer (CRPC) to supraphysiologic androgen, but current BAT uses testosterone (T), which broadly activates wild-type androgen receptor (AR) in normal androgen-responsive tissues and can cause systemic androgenic effects. 5β-Dihydrotestosterone (5β-DHT), a naturally occurring T metabolite, has been considered androgenically inactive because of weak wild-type AR activity.
Read the full summary ↓
Here, we examined whether 5β-DHT and related 5β-reduced metabolites activate mutant AR signaling and reproduce BAT-like growth suppression. METHODS Six 5β-reduced T metabolites were evaluated in C4-2 and LNCaP prostate cancer cells under androgen-depleted and BAT-like conditions. AR dependence and mutant-specific activity were assessed using enzalutamide, AR-null PC-3 cells, and PC-3 cells expressing AR-W742C or AR-H875Y. Cell proliferation, AR-responsive reporter activity, RT-qPCR, RNA sequencing with gene set enrichment analysis, immunoblotting, and senescence-associated β-galactosidase staining were used to characterize ligand responses. RESULTS At nanomolar concentrations, 5β-DHT and 3β-etiocholanediol (3β-ecdiol) induced AR target genes and promoted AR-dependent C4-2 and LNCaP growth, although less potently than T. RNA sequencing showed that both metabolites activated the T-regulated AR transcriptional program with smaller differentially expressed gene footprints. At high concentrations, 5β-DHT, but not the weaker agonist 3β-ecdiol or progesterone-class steroids, suppressed C4-2 and LNCaP proliferation. High-dose 5β-DHT also activated AR and suppressed growth in PC-3 cells expressing AR-W742C or AR-H875Y, whereas AR-null PC-3 cells were unaffected. High-dose 5β-DHT enriched androgen-response and senescence programs, suppressed G2M, E2F, and MYC-associated pathways, increased p21, p27, and p57, reduced RB phosphorylation and SKP2, and induced senescence-associated β-galactosidase activity.
This dataset
Open GSE339459 in finder → Find more human RNA-seq datasets → Prostate cancer landscape →
Download · which file do I need?

Direct links to NCBI and ENA, 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, or the whole study as GSE339459_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1498880 and SRA study SRP720242. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
10 conditions, mostly in triplicate
C4-2, vehicle (ethanol), csFBS, 24 h, biol ×3 C4-2, testosterone 10 nM, csFBS, 24 h, biol ×3 C4-2, 5beta-DHT 10 nM, csFBS, 24 h, biol ×3 C4-2, 3beta-ecdiol 10 nM, csFBS, 24 h, biol ×3 C4-2, vehicle (ethanol), 10% FBS, Day 1 (24 h… ×3 C4-2, testosterone 100 nM, 10% FBS, Day 1 (24… ×3 C4-2, 5beta-DHT 100 nM, 10% FBS, Day 1 (24 h)… ×3 C4-2, vehicle (ethanol), 10% FBS, Day 3 (72 h… ×3 +2 more

Supports a between-group comparison across 30 samples.

How we read this: 10 replicated groups read from 30 sample titles; they account for 30 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
More Prostate cancer datasets

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