Related Experiment Video
Updated: May 6, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Dexamethasone inhibits androgen receptor-negative prostate cancer cell proliferation via the GR-FOXO3a-GAS5 axis
Jieping Hu1, Yanyan Hong2, Xun Xie1
1Department of Urology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, China.
Background:
Studies have shown that glucocorticoid receptor (GR) has inconsistent effects on the proliferation of prostate cancer cells, we found dexamethasone inhibited the proliferation of androgen receptor-negative prostate cancer cells, but the underlying mechanisms remain to be illustrated.
Methods:
GR expression and its prognosis role were analyzed based on the TCGA dataset. Bioinformatic analysis was performed to identify the candidate of GR downstream, which includes FOXO3a. After overexpressing FOXO3a in PC-3 cells, cell counting kit-8 (CCK-8) and migration assays were performed to evaluate cell proliferation and migration ability. Regulation of FOXO3a on GAS5 was also analyzed by JASPAR and PCR.
Results:
GR had low expression in prostate cancer and predicted poor prognosis. FOXO3a was identified as the downstream of GR to inhibit the proliferation of prostate cancer cells. Moreover, FOXO3a directly induces GAS5 expression, forming the GR-FOXO3a-GAS5 signaling pathway.
Conclusion:
Our study showed that GR played a role as a tumor suppressor gene in androgen receptor-negative prostate cancer cells via the GR-FOXO3a-GAS5 axis. Our results suggested patients with prostate cancer should be classified and develop a treatment plan according to the expression of AR and GR.
Insights
Glucocorticoid receptor (GR) acts as a tumor suppressor in prostate cancer by inhibiting cell proliferation via the FOXO3a-GAS5 pathway. This suggests classifying patients by androgen receptor (AR) and GR expression for tailored treatment plans.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Glucocorticoid receptor (GR) exhibits variable effects on prostate cancer cell proliferation.
- Dexamethasone demonstrates inhibitory effects on androgen receptor-negative prostate cancer cells, necessitating mechanistic elucidation.
Purpose of the Study:
- To investigate the role of GR in prostate cancer, particularly in androgen receptor-negative cells.
- To identify downstream targets of GR and elucidate the underlying mechanisms of its anti-proliferative effects.
Main Methods:
- TCGA dataset analysis for GR expression and prognostic value.
- Bioinformatic identification of GR downstream targets, including FOXO3a.
- In vitro assays (CCK-8, migration) to assess cell proliferation and migration after FOXO3a overexpression in PC-3 cells.
- Analysis of FOXO3a regulation on GAS5 expression using JASPAR and PCR.
Main Results:
- Low GR expression in prostate cancer correlates with poor prognosis.
- FOXO3a identified as a downstream mediator of GR, inhibiting prostate cancer cell proliferation.
- FOXO3a directly induces GAS5 expression, establishing the GR-FOXO3a-GAS5 signaling pathway.
Conclusions:
- GR functions as a tumor suppressor in androgen receptor-negative prostate cancer via the GR-FOXO3a-GAS5 axis.
- Prostate cancer patient stratification based on AR and GR expression is recommended for personalized treatment strategies.
More Related Videos
Related Concept Videos
02:38Mitogens and the Cell Cycle
02:23Abnormal Proliferation