Related Experiment Video
Updated: Mar 20, 2026

MicroRNA Detection in Prostate Tumors by Quantitative Real-time PCR qPCR
Published on: May 16, 2012
TRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer
Anna C Groner1, Laura Cato1, Jonas de Tribolet-Hardy1
1Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Abstract:
Androgen receptor (AR) signaling is a key driver of prostate cancer (PC). While androgen-deprivation therapy is transiently effective in advanced disease, tumors often progress to a lethal castration-resistant state (CRPC). We show that recurrent PC-driver mutations in speckle-type POZ protein (SPOP) stabilize the TRIM24 protein, which promotes proliferation under low androgen conditions. TRIM24 augments AR signaling, and AR and TRIM24 co-activated genes are significantly upregulated in CRPC. Expression of TRIM24 protein increases from primary PC to CRPC, and both TRIM24 protein levels and the AR/TRIM24 gene signature predict disease recurrence. Analyses in CRPC cells reveal that the TRIM24 bromodomain and the AR-interacting motif are essential to support proliferation. These data provide a rationale for therapeutic TRIM24 targeting in SPOP mutant and CRPC patients.
Insights
Speckle-type POZ protein (SPOP) mutations in prostate cancer (PC) stabilize TRIM24, promoting cancer growth. Targeting TRIM24 offers a new therapeutic strategy for castration-resistant prostate cancer (CRPC).
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Androgen receptor (AR) signaling drives prostate cancer (PC) progression.
- Androgen-deprivation therapy is often transiently effective, leading to castration-resistant prostate cancer (CRPC).
- Speckle-type POZ protein (SPOP) mutations are recurrent drivers in PC.
Purpose of the Study:
- To investigate the role of TRIM24 in SPOP-mutant prostate cancer.
- To determine the therapeutic potential of targeting TRIM24 in CRPC.
Main Methods:
- Analysis of TRIM24 protein levels in primary PC and CRPC tissues.
- Investigating the functional interaction between SPOP, TRIM24, and AR signaling.
- Assessing the impact of TRIM24 inhibition on CRPC cell proliferation.
Main Results:
- SPOP mutations stabilize TRIM24, enhancing AR signaling and promoting proliferation in low androgen conditions.
- AR and TRIM24 co-activated genes are significantly upregulated in CRPC.
- TRIM24 protein expression increases from primary PC to CRPC.
- TRIM24 levels and an AR/TRIM24 gene signature predict disease recurrence.
- TRIM24's bromodomain and AR-interacting motif are essential for CRPC cell proliferation.
Conclusions:
- TRIM24 is a key mediator in SPOP-mutant CRPC progression.
- TRIM24 represents a promising therapeutic target for SPOP-mutant and CRPC patients.
More Related Videos
Related Concept Videos
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
mTOR Signaling and Cancer Progression
Eukaryotic Transcription Activators
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Abnormal Proliferation
Master Transcription Regulators

