Dataset Information

Transcriptomic profiling of LNCaP/C4-2 cells under stepwise androgen receptor inhibition

ABSTRACT: This study presents transcriptomic profiling of human prostate cancer cell lines under stepwise androgen receptor (AR) inhibition. LNCaP and C4-2 cells were cultured under untreated conditions, androgen deprivation using charcoal-stripped serum, long-term exposure to the first-generation AR antagonist bicalutamide, or long-term exposure to the second-generation AR antagonist enzalutamide. Drug-resistant cell populations were generated through gradual dose escalation. The neuroendocrine prostate cancer cell line NCI-H660 was included as a reference. Bulk RNA sequencing was performed for three biological replicates per condition. The dataset provides a resource for investigating transcriptional responses to progressive AR suppression and adaptive changes associated with AR-targeted therapies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE315550 | GEO | 2026/01/07

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Androgen receptor (AR)-targeting prostate cancer drugs, which are predominantly competitive ligand binding domain (LBD)-binding antagonists, are inactivated by common resistance -mechanisms. It is important to develop next-generation mechanistically-distinct drugs to treat castration- and drug- resistant prostate cancers. Here, we describe a second-generation AR pan-antagonist (UT-34) that degrades the AR and AR splice variants. UT-34 inhibits the wild-type and LBD mutant ARs comparably and inhibits the in vitro proliferation and in vivo growth of enzalutamide-sensitive and resistant prostate cancer xenografts. In preclinical models, UT-34 induced the regression of enzalutamide-resistant tumors at doses when the AR is degraded; but, at lower doses when the AR is just antagonized, it inhibits, without shrinking, the tumors. This indicates that degradation might be a prerequisite for tumor regression. Mechanistically, UT-34 promotes a conformation that is distinct from the LBD-binding competitive antagonist, enzalutamide, and degrades the AR through the ubiquitin proteasome mechanism. UT-34 has a broad safety margin and exhibits no cross-reactivity with G-Protein Coupled Receptor, kinase, and nuclear receptor family members. Collectively, UT-34 exhibits the properties necessary for a next-generation prostate cancer drug. MR49F cells (n=3-4/group) were maintained in charcoal-stripped serum containing medium for 48 hours and treated with vehicle, 0.1 nM R1881, or 10 uM of UT-34 in combination with 0.1 nM R1881. Twenty four hours after treatment, the cells were harvested, RNA was isolated and expression of genes was measured using microarray (Affymetrix Clarion S) UT-34 is a selective androgen receptor degrader that degrades and antagonizes the AR. UT-34 binds to the AF-1 domain of the AR and degrades the AR through ubiquitin proteasome pathways. The transcriptome study was performed to evaluate the ability of UT-34 to antagonize the enzalutamide-resistant AR function.

Dataset Information

Transcriptomic profiling of LNCaP/C4-2 cells under stepwise androgen receptor inhibition

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets