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Updated: Jul 14, 2026

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
Published on: December 19, 2018
DJ-1 binds androgen receptor directly and mediates its activity in hormonally treated prostate cancer cells
J Erin Tillman1, Jialing Yuan, Guangyu Gu
1Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232-2765, USA.
Abstract:
The oncogene DJ-1 has been associated with multiple cancers, including prostate cancer, where it can be stabilized by androgens and antiandrogens. However, little data exist on the expression pattern and function of DJ-1 in prostate cancer. To address the function of DJ-1 in prostate, a yeast two-hybrid screen was done to identify novel DJ-1 binding proteins. The androgen receptor (AR) was identified and confirmed as a DJ-1 binding partner. This is the first evidence that DJ-1 directly interacts with AR. We also show that modulation of DJ-1 expression regulated AR transcriptional activity. Importantly, both the subcellular localization of DJ-1 and the interaction with AR are regulated by androgens and antiandrogens. Additionally, immunohistochemical staining on two human prostate cancer tissue arrays was done providing the first large-scale expression analysis of DJ-1 in prostate. DJ-1 expression did not change with Gleason pattern but increased after androgen deprivation therapy, indicating that it may be involved in the development of androgen independence. These data provide a novel mechanism where DJ-1-mediated regulation of AR may promote the progression of prostate cancer to androgen independence.
Insights
The oncogene DJ-1 interacts with the androgen receptor (AR) in prostate cancer. DJ-1 regulation by hormones may drive cancer progression to androgen independence.
Area of Science:
- Oncology
- Molecular Biology
- Urology
Background:
- The oncogene DJ-1 is implicated in various cancers.
- DJ-1 stabilization by androgens and antiandrogens is known in prostate cancer.
- Limited data exist on DJ-1's role and expression in prostate cancer.
Purpose of the Study:
- To identify novel DJ-1 binding proteins in prostate cancer.
- To investigate the functional interaction between DJ-1 and the androgen receptor (AR).
- To analyze DJ-1 expression patterns in human prostate cancer tissues.
Main Methods:
- Yeast two-hybrid screening to identify DJ-1 interacting proteins.
- Confirmation of DJ-1 and AR interaction.
- Assessment of AR transcriptional activity modulation by DJ-1.
- Immunohistochemical staining of DJ-1 in human prostate cancer tissue arrays.
Main Results:
- The androgen receptor (AR) was identified as a novel DJ-1 binding partner.
- DJ-1 directly interacts with AR, and this interaction is modulated by androgens/antiandrogens.
- DJ-1 expression increases after androgen deprivation therapy, suggesting a role in androgen independence.
- DJ-1 expression levels did not correlate with Gleason pattern.
Conclusions:
- DJ-1 directly interacts with the androgen receptor (AR) in prostate cancer.
- DJ-1 regulates AR transcriptional activity, with localization and interaction influenced by androgens/antiandrogens.
- Increased DJ-1 expression post-androgen deprivation suggests a mechanism promoting prostate cancer androgen independence.
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