Related Experiment Video
Updated: Jan 31, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Low Expression of the Androgen-Induced Tumor Suppressor Gene PLZF and Lethal Prostate Cancer
Konrad H Stopsack1, Travis Gerke2, Svitlana Tyekucheva3,4
1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Background:
4%-9% of prostate cancers harbor homozygous deletions of the androgen-induced tumor suppressor gene, promyelocytic leukemia zinc finger (PLZF, ZBTB16). PLZF loss induces an in vitro phenotype of castration resistance and enzalutamide resistance. The association of low expression of PLZF and clinical outcomes is unclear.
Methods:
We assessed PLZF mRNA expression in patients diagnosed with primary prostate cancer during prospective follow-up of the Health Professionals Follow-up Study (HPFS; n = 254) and the Physicians' Health Study (PHS; n = 150), as well as in The Cancer Genome Atlas (n = 333). We measured PTEN status (using copy numbers and IHC) and transcriptional activation of the MAPK pathway. Patients from HPFS and PHS were followed for metastases and prostate cancer-specific mortality (median, 15.3 years; 113 lethal events).
Results:
PLZF mRNA expression was lower in tumors with PLZF deletions. There was a strong, positive association between intratumoral androgen receptor (AR) signaling and PLZF expression. PLZF expression was also lower in tumors with PTEN loss. Low PLZF expression was associated with higher MAPK signaling. Patients in the lowest quartile of PLZF expression compared with those in the highest quartile were more likely to develop lethal prostate cancer, independent of clinicopathologic features, Gleason score, and AR signaling (odds ratio, 3.17; 95% confidence interval, 1.32-7.60).
Conclusions:
Low expression of the tumor suppressor gene PLZF is associated with a worse prognosis in primary prostate cancer.
Impact:
Suppression of PLZF as a consequence of androgen deprivation may be undesirable. PLZF should be tested as a predictive marker for resistance to androgen deprivation therapy.
Insights
Low expression of the promyelocytic leukemia zinc finger (PLZF) gene in prostate cancer correlates with a worse prognosis. This finding suggests PLZF may serve as a predictive marker for treatment resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Prostate cancers (4%-9%) exhibit homozygous deletions of the tumor suppressor gene, promyelocytic leukemia zinc finger (PLZF).
- Loss of PLZF is linked to in vitro castration and enzalutamide resistance.
- The clinical relevance of low PLZF expression in prostate cancer remains unclear.
Purpose of the Study:
- To investigate the association between PLZF mRNA expression and clinical outcomes in primary prostate cancer.
- To explore the relationship between PLZF expression, PTEN status, and MAPK pathway activation.
Main Methods:
- Assessed PLZF mRNA expression in independent patient cohorts (HPFS, PHS, TCGA).
- Measured PTEN status and MAPK pathway activation.
- Followed patients for metastases and prostate cancer-specific mortality.
Main Results:
- PLZF expression was lower in tumors with PLZF deletions, PTEN loss, and higher MAPK signaling.
- Strong positive association observed between androgen receptor signaling and PLZF expression.
- Lowest PLZF expression quartile correlated with increased risk of lethal prostate cancer (OR, 3.17).
Conclusions:
- Low PLZF expression is associated with a worse prognosis in primary prostate cancer.
- PLZF suppression may be detrimental under androgen deprivation.
- PLZF warrants investigation as a predictive marker for resistance to androgen deprivation therapy.
Related Concept Videos
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
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...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
02:35Chromatin Position Affects Gene Expression
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
01:42What is Gene Expression?
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
01:36What is Gene Expression?
01:58Cell Specific Gene Expression