Category: Basic Science: Oncology

MP1-12 - TRIM36, a novel androgen-responsive gene, enhances anti-androgen efficacy against prostate cancer by inhibiting MAPK/ERK signaling pathways

Thu, Sep 20
4:00 PM - 6:00 PM

Introduction & Objective :

Hormone therapy drugs, such as bicalutamide and enzalutamide, directed against prostate cancer focus on androgen receptor (AR) signaling and are initially effective, but the disease progresses to lethality as resistance to these drugs develops. A method to prolong the drug response time and improve the drug efficacy is still unavailable. TRIM36 was reported as a novel androgen signaling target gene and is upregulated in prostate cancer. 


Methods : TRIM36 expression has been detected by mRNA microarray analysis, quantitative reverse transcription (qRT-PCR), Western blotting and Liquid chromatography-Mass Spectrum (LC-MS/MS) in matched prostate cancer and adjacent normal tissues, and prostate cell lines RWPE-1, C4-2, LNCaP, DU145, PC3. A total of 95 cases of prostate cancer after radical prostatectomy were analysed in a tissue microarray (TMA) for TRIM36 and androgen receptor (AR) protein expression. Prostate cancer cells stably expressing and shRNAs knockdown TRIM36 were used for CCK-8 assay, clone formation assay and xenograft. Androgen regulation was examined by ChIP, dual-luciferase reporter assay, qRT-PCR and Western blot analysis.


Results : n this study, we found that 63.4% (64/95) of PCa in TMA expressed the TRIM36 protein. Interestingly, patients with negative TRIM36 expression had a shorter biochemical recurrence-free survival. TRIM36 expression was significantly associated with the Gleason score (P=0.005), delayed prostate cancer cell cycle progression and inhibited cell proliferation in vitro and in vivo, and these effects were mediated via inhibition of the MAPK/ERK phosphorylation pathway. Remarkably, we found that rescuing the expression of TRIM36 during anti-androgen therapy could improve the drug efficacy. 


Conclusions :

Collectively, TRIM36 is a novel androgen-responsive gene, and it dramatically enhanced the efficacy of anti-androgen drugs against prostate cancer.

Jie Li

Vice director of Department of Urology
The first affiliated hospital of Nanjing Medical University
Nanjing, Jiangsu, China (People's Republic)

Chao Liang


Nanjing, Jiangsu, China (People's Republic)

Shangqian Wang


Nanjing, Jiangsu, China (People's Republic)

Bianjiang Liu


Nanjing, Jiangsu, China (People's Republic)

Gong Cheng


Nanjing, Jiangsu, China (People's Republic)

Chao Qin


Nanjing, Jiangsu, China (People's Republic)

Pengfei Shao


Nanjing, Jiangsu, China (People's Republic)

Zengjun Wang


Nanjing, Jiangsu, China (People's Republic)