NF-κB and androgen receptor variant expression correlate with human BPH progression

Area of Science:

• Urology
• Oncology
• Molecular Biology

Background:

• Benign prostatic hyperplasia (BPH) is a progressive disease often associated with inflammation.
• Inflammation and nuclear factor-kappa B (NF-κB) pathway activation are implicated in BPH progression and resistance to 5α-reductase inhibitor (5ARI) therapy.

Purpose of the Study:

• To investigate the role of NF-κB activation and androgen receptor variant (AR-V) expression in BPH.
• To determine the effect of NF-κB activation on AR-V7 expression and 5ARI resistance.

Main Methods:

• NF-κB activation and AR-V expression were quantified in prostate tissue samples from BPH patients.
• Human prostate cell lines were used to study the effects of NF-κB activation on AR-FL, AR-V, cellular growth, and differentiation.

Main Results:

• Canonical NF-κB signaling and AR-variant 7 (AR-V7) expression were upregulated in advanced BPH.
• NF-κB activation in prostate cells led to increased AR-FL and AR-V7 expression, ligand-independent AR activation, and maintained cell viability under 5ARI treatment.

Conclusions:

• NF-κB activation and AR-V7 expression are associated with increased BPH severity.
• NF-κB can induce AR-V7 expression, leading to 5ARI resistance, suggesting a mechanism for treatment resistance in BPH patients.